148 B.B.S. AND DISEASE

sudden muscular exertion such as coughing rupturesthe muscle ; sometimes the symptoms come oninsidiously. Heart failure and pregnancy are two

important general causes, while typhoid fever andinfluenza may both weaken the muscle locally byproducing the hyaline degeneration that is associatedwith the name of ZENKER. Diagnosis is often diffi-cult, especially when there is no history of traumaor of a sudden onset of the symptoms, and somecause of local peritonitis such as appendicitis orcholecystitis is usually suspected. There is alsoanother class of case in which hsematoma maybe found and in which a special diagnostic difficultymay arise. A local predisposing cause of haema-toma of the rectus is a previous operation throughit or near it, which by setting up adhesions inter-feres with the mechanism by which the muscle isallowed to move independently of the vessels ; inthis way a sudden contraction of the muscle mayproduce a shearing stress which will tear theadherent vessel. A tense, tender, irreducible

lump appears in the region of the old scar, and thepicture of strangulated incisional hernia is fairlycomplete.

If the diagnosis of haematoma of the rectus canbe made with confidence no operative treatment isadvisable provided the bleeding has stopped.Usually, however, the diagnosis is established onlywhen the lesion is exposed, and in these cases theclot should be turned out, the bleeding vesselsligatured, and the torn muscle repaired. Rarely,in cases of typhoid and influenza, the haematomabecomes infected by the specific organism and thesequel is an abscess.

B.B.S. AND DISEASEOF late years increasing attention has been

paid to the bisulphite-binding substances (B.B.S.)of the blood in relation to vitamin-BI deficiencyand other conditions encountered in clinicalmedicine. So far as vitamin BI is concerned theexperimental foundation for this work was laid inobservations in the department of biochemistry atOxford, the details of which appeared in a lectureby Prof. R. A. PETERS, F.R.S., published in thisjournaI.I It suffices now to say that PETERS andH. M. SINCLAIR, and R. H. S. THOMPSON gaveproof by in-vitro respiration studies with thebrains of pigeons that in vitamin-BI deficiency thereis a specific accumulation of the intermediary carbo-hydrate metabolite pyruvic acid (CH3CO.COOH),whereas in the presence of this vitamin pyruvicacid does not accumulate. The implication ofthis work is that pyruvic acid is a normal

stage in oxidationof carbohydrate which accumu-lates because, in the absence of vitamin Bl, furtheroxidation cannot take place. Developing thisstory THOMPSON and R. E. JOHNSON found thatin animals suffering from vitamin-BI deficiencypyruvic acid collects abnormally in the blood,disappearing upon cure of the animal. It shouldbe mentioned, however, that there is no evidencethat pyruvic acid under these conditions is actuallytoxic. Its presence can be demonstrated as an

1 Peters, R. A., Lancet, 1936, 1, 1161.

increase in the value of B.B.S. in the blood, andthough the property of binding bisulphite is sharedwith other ketonic and aldehyde substances, thereis a clear proof that in the case of vitamin-B1deficiency it is actually pyruvic acid that accumu-lates. The work mentioned shares its place withother observations upon substances of this type;for instance, PI SURFR2 has found pyruvic acidtogether with methyl glyoxal in certain urines,notably those of diabetics. Further, as PETERSpointed out, A. GEIGER and colleagues haveclaimed the presence of methyl glyoxal in theurines of infants suffering from vitamin-B1deficiency.

Clinical observation in this country led to nofinding of increased B.B.S. in the blood except incases of diabetes where increases might be expectedto be due to aceto-acetic acid.l But in the Orient,at Shanghai, in excellent work now unfortunatelysuspended, PLATT and Lu obtained evidence insome detail that the results of the animal experi-ments were applicable to beri-beri in man. Theybelieved, however, that substances other than

pyruvic acid, which were estimated by the B.B.S.method, were also increased in the blood, andSHINDO 4 claims the identification of acetalde.

hyde in the blood of beri-beri patients. Quiterecently TAYLOR, WEiss, and WiLEiNS 5 have

reported upon the examination of the bloods of avariety of clinical conditions. Finding that thenormal range for B.B.S. is 4-71-0 mg. per100 c.cm. of blood (calculated as pyruvic acid),they consider that all cases showing 6 mg.+ per100 c.cm. blood can be deemed to have a raisedB.B.S. value. According to this criterion, raisedB.B.S. were found in 10 out of 19 cases of uncom-

pensated organic heart disease, 18 out of 23 casesof untreated vitamin-Bl deficiency, 6 out of 9 casesof infectious disease, 7 out of 7 cases of diabeteswith acidosis, and 2 out of 4 cases of nephro-sclerosis. Treatment of the heart disease led to

improvement in the B.B.S., and treatment of thevitamin-Bl deficiency consistently reduced it. Ofsubstances at present known the most likely tobind bisulphite are acetone and aceto-acetic acid,and in the diabetics there was evidence that theincreased B.B.S. value was due largely to these,though pyruvic acid was also demonstrated in theurine in confirmation of PI SuNER and FARRAN ;it was the investigators’ view that the increasedB.B.S. was an accurate index of the clinicalseverity of the diabetes. In heart disease, theraised B.B.S. value was often not due to theketosis alone. WiLsoON and GHosH,6 in a paperinspired by the work of PLATT and Lu, find thatB.B.S. is increased in India in epidemic dropsy,anaemia, and splenomegaly as well as diabetes ;the greatest increase (up to 8 mg.) was in epidemicdropsy.

It is clear, as TAYLOR and his colleagues say,2 Pi Suñer, A., and Farrán, M., C.R. Soc. Biol. Paris, 1936,

122, 859.3 Platt, B. S., and Lu, G. D., Quart. J. Med. 1936, n.s. 5, 355.

4 Shindo, T., Hoppe-Seyl. Z. 1937, 247, iii.5 Taylor, F. H. L., Weiss, S., and Wilkins, R. W., J. clin.

Invest. November, 1937, p. 833.6 Wilson, H. E. C., and Ghosh, B. K., Indian med. Gaz. 1937,

72, 147.

149TUBERCULOUS MENINGITIS

that the increase in B.B.S. cannot be used byitself as a diagnostic test of any one disease.Nevertheless, when combined with attempts todefine chemically the substances present, it maythrow light upon certain aspects of disorderedfunction. PLATT has already shown its value as anindication of the action of vitamin Bl in beri-beri.

TUBERCULOUS MENINGITIS

THE pathogenesis of tuberculous meningitiscontinues to inspire both speculation and research.In 1935 we reviewed 1 it in the light of muchwork published in the two previous years, especiallyon the relation of tuberculous meningitis to miliarytuberculosis, and on the possibility of recovery.We drew attention to the difficulty of makinga certain diagnosis of meningitis during life, andsuggested that the accepted interpretation of

changes in the cerebro-spinal fluid might requirereconsideration. At that time the old view thattuberculous meningitis is the immediate and

typical result of miliary tuberculosis had been

severely shaken by the work of RICH andMCCORDOCK, who maintained that meningitisnever follows directly from miliary tuberculosisbut is always preceded by the formation of caseoustuberculomata in the brain or meninges. Some ofthe communications that we quoted, especially oneby MORRIS SIEGEL, seemed to support this hypo-thesis, as does the consistent failure of animal

experiment to produce meningitis by inoculationof tubercle bacilli into the blood stream. Duringthe past two years further attempts have beenmade to arrive at the facts, but the results havebeen by no means uniform. The evidence thatA. B. RAGINS obtained from examination of47 brains did not bear out the opinions of RICHand MCCORDOCK, but pointed to a direct hsemato-genous spread (in 38 of the 47). C. RADMANN,working on a much smaller material, concludedthat meningitis occurs both with and without theprevious formation of solitary tubercles.

Stimulated by this divergence of opinion on asomewhat fundamental question, Dr. A. R.MACGREGOR and Dr. C. A. GREEN 2 of Edinburghset themselves the task of answering it by a com-prehensive study of 112 brains. They arguedthat if RICH and McCoRDOCE’s conception holdsgood, even in a proportion of cases, some victimsof tuberculous meningitis must have had an

infection of the brain with focal deposits at someprevious time. It was therefore desirable toexamine brains of sufferers not only from mening-itis but from tuberculosis of other organs. When

possible the spinal cords were also examined, andthe cerebro-spinal fluid was investigated for bacilli.A search for tubercle bacilli was also made in thefluids of 45 patients with suggestive symptomswho did not die of meningitis. The report showsthat of the 88 brains examined in which meningitiswas present tuberculous infection antecedent tothe meningitis was found in 74 ; and in 4 othersthere was disease of the spine. Thus in 88 per

1 Lancet, 1935, 2, 950.2 J. Path. Bact. November, 1937, p. 613.

cent. there was evidence of old foci in or adjacentto the central nervous system. It is of interestthat while foci were found in the meninges alone,in the brain alone, and in both together, the firstshowed the greatest number. Though thereremain 10 cases in which careful examinationrevealed no antecedent focus, the conclusion maybe drawn that tuberculous meningitis is mostoften preceded by a localised infection. The

presence of a focus, however, does not prove thatit was the source of the meningitis, and MACGREGORand GREEN accordingly sought confirmation byhistological examination of each specimen, accept-ing as probable sources only those foci that werenot encapsuled, were adjacent to the meningealsurface, and were surrounded by recent exudate.By these criteria 10 of the 78 cases were rejected,58 were regarded as certain, and 6 as very probable.From their histological observations the investi-

gators are convinced that meningitis does notarise at the base of the brain, where it is most

typically found in well-developed cases. Thedistribution of the exudate depends in the firstinstance on the situation of the initial lesion,though later it is concentrated in the basalcisterns.

While the great majority of specimens examinedby MACGREGOR and GREEN supported RiCH andMCCoRDOCK’s view, there were 23 that did not.Further consideration made it clear, however, thatneither did they support the hypothesis of heemato-genous spread ; for in 8 of them miliary tubercu-losis was absent and in 7 it was very slight. Ofthe 25 brains that did not show meningitis 11contained tuberculous lesions : these subjects weremostly children ; miliary tubercle was severe in 7of them and was confined to the nervous systemin 3. The cerebro-spinal fluid (usually obtainedpost mortem by cisternal puncture) was examinedin 20 cases of this group, and tubercle bacilli weredemonstrated in 10. It is to be noted that bacilliwere found in the fluid of 2 subjects whose brainsshowed no tuberculous lesion. Besides these

post-mortem examinations an investigation wasmade of the cerebro-spinal fluid of 45 patients,9 suffering from active tuberculosis and the restreacting to tuberculin. None of them died or

developed meningitis ; in all of them lumbar

puncture was performed because of symptoms ofmeningeal irritation. In 3 of them tubercle bacilliwere recovered by animal inoculation and in 2others the cytological changes suggested meningitis.MACGREGOR and GREEN’s explanation is that thelumbar punctures and the symptoms occasioningthem coincided with the formation of tuberculousfoci in the nervous system. While the result oftheir work leads the Edinburgh workers to supportthe view of RICH and MCCORDOCK they recognisethat this does not account for the close associationfound between miliary tuberculosis and tuberculousmeningitis. The possible ways by which this

difficulty may be overcome are shrewdly discussed,and alternative explanations are submitted.

Perhaps the most interesting and most novel ofthese is that the meningitis may at times giverise to the miliary tubercles.