799

INFECTIOUS DISEASES AND THE BRAIN

THE LANCET

LONDON : SATURDAY, .APRIL 14, 1934

IT sometimes happens in science, and especiallyin medical science, that what has been regarded asan axiom turns out to have been a hasty generalisa-tion. For example, it has long been assumedthat the symptoms characteristic of all fevers-such as apathy, insomnia, raised temperature,metabolic disturbances, vasomotor collapse, andeventually death-are due to disturbances of thebrain centres produced directly by bacterial toxins.Prof. FRIEDEMANN and Dr. ELKELES, in the paperconcluded in our present issue, throw doubt onthe validity of this assumption.Whether bacteria] toxins do or do not act on the

nerve-cells of the brain must obviously depend inthe first place on whether they are able to reachthese cells, although other factors such as chemicalaffinity will play a secondary part. The problemis bound up, therefore, with the problem of theexchange of substances between blood and brain.The work of the last few years has shown that thisexchange is regulated by a selective mechanism,described by continental writers as the " barrierehemato-encephalique

" or

" Bluthirnschranke," orin English as the " blood-brain barrier," or B.B.B.In the brain, as in other organs, the selectivemechanism is localised in the walls of the capil-laries ; in this case it is in the cerebral capillaries,and not, as was formerly thought, in the choroidplexus and the meningeal vessels. FBIBDBMANN andELKELES have devised new methods of testing thepermeability of this barrier for various toxins, andtheir results show clearly that the toxins differ

among themselves in the facility with which theypass through it. Those of the botulinus, diphtheria,and tetanus organisms, for instance, do not passthe blood-brain barrier at all (tetanus is, of course,exceptional in reaching the brain by anotherroute, through the peripheral nerves). On theother hand, there are some, such as lamb-dysenterytoxins and cobra venom, which definitely do gothrough the barrier. The two groups differ alsoin another respect : those that are able to passthe B.B.B. produce their lethal effect rapidly,whereas those that cannot pass the B.B.B. requirea period of incubation. If this tentative generalisa-tion should be found to hold good for all toxins, itwill mean that few bacterial toxins act on thebrain ; for we know that most of them require aperiod of incubation. On further inquiry into theproperty of the toxins which govern their abilityto pass the blood-brain barrier, it was found thatthose that could not pass the barrier carry a nega-tive charge, while those that could pass it are eitherneutral or positively charged. It follows from thisthat differences in the length of the incubation

period characteristic of different toxins depend ontheir electrical charge.The subject is highly technical and may at first

sight seem somewhat remote from practice. Prof.FRIEDEMANN, however, is not only a laboratoryworker but also a clinical authority on the treat-ment of infectious diseases, and his investigationhas clearly arisen as an attempt to account for theclinical features of these diseases and also forfailures in their treatment. The handling ofdiphtheria, for example, is to some extent basedon the assumption that the toxin has a directlocalised action on the brain and also on the heartmuscle, and FniBDEMANN’s treatment of it has beenprofoundly influenced by the results of his labora-tory studies. Since vasomotor collapse, which isan outstanding feature of diphtheria, has beenascribed in the past to a paralysis of the vasomotorcentre, it has been treated by drugs expected tostimulate the centre ; though FRIEDEMANN sayshe has never seen any good come from suchremedies. But if diphtheria toxin does not reachthe brain, the vasomotor collapse must be of

peripheral origin and must be treated accordingly.With this in view he instituted in Berlin its manage-ment by means of hot baths, and he claims that" the effects of this treatment are striking evenin the most severe cases, and not to be comparedwith those of drugs. Symptoms are improved atonce and remain so for hours." According to hisnew conception of the pathogenesis of infectiousdiseases the toxins of many other infections shouldproduce their effects peripherally and not centrally,and it may be expected that a better under-

standing of their action will lead to further improvement in their treatment. The Medical ResearchCouncil is to be congratulated on having enabledProf. FsiEDEMANN to continue his work byproviding him with laboratory facilities inLondon;

A GENERAL MEDICAL SERVICETHE official report of the annual meeting in

Llandudno last September of the National Con-ference of Friendly Societies contains a scheme fora general medical service submitted by its executivecommittee. The services proposed were compre-hensive, covering treatment by a family doctor,medicines, nursing in the home, provision of

consultants, specialists and auxiliary means of

diagnosis (presumably pathological) through thegeneral practitioner, home hospitals in which

general practitioners would treat their own patientsand meet one another in friendly consultation,residential accommodation in hospitals, sanatoria,and convalescent homes, and such other medicaland allied services as may from time to time be

arranged. In addition to insured persons as definedin the National Health Insurance Acts, persons whowould be insured but for the fact that they arefollowing excepted employments would becomecompulsory contributors, and voluntary participa-tion would be extended to all members of friendlysocieties. Further, dependants of all such personswould be brought into the scheme and an arrange-