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LOOKING FOR THE LEAK
134
the synthetic penicillins and the cephalexin/cephaloridine group would come under the same roof. The combined research budgets of the two companies total less than E10 million, and this looks rather small beside the sums that the Swiss and American giants are putting in; however, the building of new laboratories suggests that research budgets would have increased in the natural order of events. These days the odds against finding a really useful new drug are lengthening, and massive research funds are no guarantee of success. Unless the whole is somehow greater than the sum of its parts the merger will be unproductive in research terms: drug companies should be prepared to allocate a substantial part of enlarged total research budgets to basic research with little prospects of short-term returns.
LOOKING FOR THE LEAK
IT is well known that Chiari described one feature of the congenital anomaly of the hind-brain called the Arnold-Chiari malformation. It is not so well known that he is credited with the first description at necropsy of an intracranial aerocele in 1884.1 Air can enter the cranium from the nasal passages, the ear, or rarely from a penetrating wound of the vault. The usual cause is trauma, and although a fistula more commonly reveals itself by escape of cerebrospinal fluid or by meningitis, an aerocele may be commoner than is realised. Such, at least, is the view of North 2 who has recorded 41 cases treated in the Royal Adelaide Hospital neurosurgical clinic since 1954. This represents the largest series published to date. Since there was cerebrospinalfluid leakage in only half the cases, aerocele may be the clue to the presence of a fistula, which will lead to meningitis in about a quarter of the cases. There may be an interval between the trauma and the development of aerocele or meningitis: the fistula may be temporarily plugged with brain and arachnoid, which may later be disturbed by minimal trauma or pressure
changes. Localisation of the dural defect can be aided by careful radiographs, including anteroposterior and lateral tomograms to show a bony defect. It would be wrong, however, to pretend that the site of a fistula is always easy to diagnose. Cerebrospinal-fluid rhinorrhoea may be intermittent, and at the time of investigation may be absent. If present, the nature of the fluid can be confirmed by testing for sugar and by introducing a dye such as phenolphthalein or indigo carmine into the lumbar theca, with recovery from the nasal discharge. Penicillin has been used similarly; and radioactive iodinated human serum-albumin has also been employed, but passes normally into mucosa, so that only a difference between the two sides is likely to be significant. It has the advantage of providing a figured measurement, but this itself depends on the vagaries of nasal secretion. The fistula may be into the middle ear from birth or as a result of later trauma. Although a traumatic fistula has a greater tendency to heal, closure is not 1. 2.
H. Z. Heilk. 1884, 5, 383. North, J. B. Br. J. Surg. 1971, 58, 826.
Chiari,
Congenital fistulas may also go through the described by Bennett,3,4 or into the from the temporal fossa. Sponsinus sphenoidal taneous rhinorrhoea through the cribriform plate may follow nasal infection, with resultant atrophy of part of the olfactory bulb, or result from extreme thinning and stretching in severe oxycephaly. Esoteric fistula: can be extremely difficult to localise. In addition to the methods already mentioned, pneumoencephalography or iophendylate (’Myodil’) has been employed. Always the difficulty is to find the small or the inter-
invariable.
inner ear,
as
mittent leak. Most iistulse are treated with a fascial graft, generous in overlap and sutured into place intradurally. Other materials have been used, but autogenous fascia lata has proved so safe and satisfactory that it remains the material of choice. Sometimes surgical exploration has to be undertaken on circumstantial evidence, and the fistula may not be found in the anterior fossa. The sella turcica, the temporal fossa, or the petrous bone will then be suspect. Surgical fistula following hypophysectomy can give rise to persistent leakage, and may be tucked under the anterior edge of the sella as viewed from above. Fortunately, many of the indications for closure of a fistula also point to its probable location-for example, an obvious fracture extending into the ethmoid roof or cribriform plate, unilateral rhinorrhoea, and unilateral anosmia. The difficult indications are meningitis (frequently pneumococcal) and, to some extent, the aerocele itself. Insertion of materials into the cranium via nose or ear carries a greater risk of infection than does the gas itself. When sugary fluid cannot be retrieved with ease, subdural air has been used from above, but the multiplicity of methods and materials reflects the low success-rate. Myringotomy (if there is fluid in the middle ear), assessment of hearing, and careful tomography can probably be as helpful in petrous cases as any other methods to distinguish a middle-fossa from a posteriorfossa source of a fistula. If the inner ear is dead, a local operation through the ear can be used to block the communication.
In
deciding whether to operate or not, the discovery nice conclusive aerocele can almost be a relief. Historically, of course, an aerocele has led to great benefit, for although it was first reported on radiography in 1913,6 it was Dandy who recognised its
of
a
diagnostic potential and developed ventriculography and encephalography as the result of seeing it in 1918.’’’7 The air may reach subdural, subarachnoid, intracerebral, or intraventricular situations, but a famous story probably concerned extradural air. In this tale, a man who had had surgical treatment by packing for a paranasal-sinus fistula eventually was left with a fistula also through the upper frontal region. He made a steady income in his local by blowing tobacco smoke through the hole in the top of his head; and it is said that he was never so chagrined as when he was cured by further surgical skill of his remaining defect. 3. 4.
Bennett, R. J. J. Laryng. 1966, 80, 1242. Bennett, R. J. ibid. 1971, 85, 169. 5. Luckett, W. H. Surgery Gynec. Obstet. 1913, 17, 237. 6. Dandy, W. E. Ann. Surg. 1918, 68, 5. 7. Dandy, W. E. Archs Surg., Chicago, 1926, 12, 949.
the synthetic penicillins and the cephalexin/cephaloridine group would come under the same roof. The combined research budgets of the two companies total less than E10 million, and this looks rather small beside the sums that the Swiss and American giants are putting in; however, the building of new laboratories suggests that research budgets would have increased in the natural order of events. These days the odds against finding a really useful new drug are lengthening, and massive research funds are no guarantee of success. Unless the whole is somehow greater than the sum of its parts the merger will be unproductive in research terms: drug companies should be prepared to allocate a substantial part of enlarged total research budgets to basic research with little prospects of short-term returns.
LOOKING FOR THE LEAK
IT is well known that Chiari described one feature of the congenital anomaly of the hind-brain called the Arnold-Chiari malformation. It is not so well known that he is credited with the first description at necropsy of an intracranial aerocele in 1884.1 Air can enter the cranium from the nasal passages, the ear, or rarely from a penetrating wound of the vault. The usual cause is trauma, and although a fistula more commonly reveals itself by escape of cerebrospinal fluid or by meningitis, an aerocele may be commoner than is realised. Such, at least, is the view of North 2 who has recorded 41 cases treated in the Royal Adelaide Hospital neurosurgical clinic since 1954. This represents the largest series published to date. Since there was cerebrospinalfluid leakage in only half the cases, aerocele may be the clue to the presence of a fistula, which will lead to meningitis in about a quarter of the cases. There may be an interval between the trauma and the development of aerocele or meningitis: the fistula may be temporarily plugged with brain and arachnoid, which may later be disturbed by minimal trauma or pressure
changes. Localisation of the dural defect can be aided by careful radiographs, including anteroposterior and lateral tomograms to show a bony defect. It would be wrong, however, to pretend that the site of a fistula is always easy to diagnose. Cerebrospinal-fluid rhinorrhoea may be intermittent, and at the time of investigation may be absent. If present, the nature of the fluid can be confirmed by testing for sugar and by introducing a dye such as phenolphthalein or indigo carmine into the lumbar theca, with recovery from the nasal discharge. Penicillin has been used similarly; and radioactive iodinated human serum-albumin has also been employed, but passes normally into mucosa, so that only a difference between the two sides is likely to be significant. It has the advantage of providing a figured measurement, but this itself depends on the vagaries of nasal secretion. The fistula may be into the middle ear from birth or as a result of later trauma. Although a traumatic fistula has a greater tendency to heal, closure is not 1. 2.
H. Z. Heilk. 1884, 5, 383. North, J. B. Br. J. Surg. 1971, 58, 826.
Chiari,
Congenital fistulas may also go through the described by Bennett,3,4 or into the from the temporal fossa. Sponsinus sphenoidal taneous rhinorrhoea through the cribriform plate may follow nasal infection, with resultant atrophy of part of the olfactory bulb, or result from extreme thinning and stretching in severe oxycephaly. Esoteric fistula: can be extremely difficult to localise. In addition to the methods already mentioned, pneumoencephalography or iophendylate (’Myodil’) has been employed. Always the difficulty is to find the small or the inter-
invariable.
inner ear,
as
mittent leak. Most iistulse are treated with a fascial graft, generous in overlap and sutured into place intradurally. Other materials have been used, but autogenous fascia lata has proved so safe and satisfactory that it remains the material of choice. Sometimes surgical exploration has to be undertaken on circumstantial evidence, and the fistula may not be found in the anterior fossa. The sella turcica, the temporal fossa, or the petrous bone will then be suspect. Surgical fistula following hypophysectomy can give rise to persistent leakage, and may be tucked under the anterior edge of the sella as viewed from above. Fortunately, many of the indications for closure of a fistula also point to its probable location-for example, an obvious fracture extending into the ethmoid roof or cribriform plate, unilateral rhinorrhoea, and unilateral anosmia. The difficult indications are meningitis (frequently pneumococcal) and, to some extent, the aerocele itself. Insertion of materials into the cranium via nose or ear carries a greater risk of infection than does the gas itself. When sugary fluid cannot be retrieved with ease, subdural air has been used from above, but the multiplicity of methods and materials reflects the low success-rate. Myringotomy (if there is fluid in the middle ear), assessment of hearing, and careful tomography can probably be as helpful in petrous cases as any other methods to distinguish a middle-fossa from a posteriorfossa source of a fistula. If the inner ear is dead, a local operation through the ear can be used to block the communication.
In
deciding whether to operate or not, the discovery nice conclusive aerocele can almost be a relief. Historically, of course, an aerocele has led to great benefit, for although it was first reported on radiography in 1913,6 it was Dandy who recognised its
of
a
diagnostic potential and developed ventriculography and encephalography as the result of seeing it in 1918.’’’7 The air may reach subdural, subarachnoid, intracerebral, or intraventricular situations, but a famous story probably concerned extradural air. In this tale, a man who had had surgical treatment by packing for a paranasal-sinus fistula eventually was left with a fistula also through the upper frontal region. He made a steady income in his local by blowing tobacco smoke through the hole in the top of his head; and it is said that he was never so chagrined as when he was cured by further surgical skill of his remaining defect. 3. 4.
Bennett, R. J. J. Laryng. 1966, 80, 1242. Bennett, R. J. ibid. 1971, 85, 169. 5. Luckett, W. H. Surgery Gynec. Obstet. 1913, 17, 237. 6. Dandy, W. E. Ann. Surg. 1918, 68, 5. 7. Dandy, W. E. Archs Surg., Chicago, 1926, 12, 949.