90ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:990-993

SHORT REPORT

Extradural application of bismuth iodoformparaffin paste causing relapsing bismuthencephalopathy: a case report with CT and MRIstudies

Rewati Raman Sharma, Ian P Cast, Robert M Redfern, Cieran O'Brien

AbstractBismuth iodoform paraffin paste (BIPP)is used in dressings in ear, nose, andthroat, dental, and neurosurgical prac-

tice. Neurotoxicity due to absorption ofbismuth from the BIPP pack is rare. It ispreventable and reversible but likely tobe fatal if unrecognised. A case of relaps-ing but reversible toxic encephalopathydue to a large extradural BIPP pack isreported in a 57 year old Caucasianwoman, operated on for a huge basal cellcarcinoma of the vertex invading theskull and extradural space. Clinical,neuroradiological (CT and MRI), andbiochemical studies are presented anddiscussed in the light of the availableliterature.

(J Neurol Neurosurg Psychiatry 1994;57:990-993)

Departments ofSurgical Neurologyand Pathology,Morriston Hospital,Morriston, SwanseaSA6 6NL, Wales, UKR R SharmaI P CastR M RedfernC O'BrienCorrespondence to:Mr Ian P Cast, Departmentof Surgical Neurology, WardE, Morriston Hospital,Morriston, SwanseaSA6 6NL, Wales, UK.Received 5 July 1993and in revised form10 January 1994.Accepted 13 January 1994

Rutherford Morrison introduced BIPP in1916.' It contains two parts of iodoform andone part of bismuth subnitrate or carbonatein a liquid paraffin base. It has many applica-tions particularly in oral, maxillofacial, ear,

nose, and throat, and neurosurgical practices.Its principle uses in neurosurgery are pack-

ing after trans-sphenoidal surgery, skull basesurgery, and chronic infective scalp wounds.The use of BIPP makes impregnated gauze

impervious to blood and body fluids ensuringlittle nutrition for bacteria to thrive in itsinterstices.2 It also has the ability to stimulategranulation tissue. Its stability in the presence

of necrotic tissue resulting in clean manage-able cavities is remarkable in our experience.

Reports of neurotoxicity after absorption ofbismuth from a BIPP pack are infrequent.34We report a case of relapsing encephalopathyafter chronic extradural application of a largeBIPP pack.

Case reportA 57 year old right handed housewife pre-sented in March 1991 with a nine month his-tory of a progressively enlarging hugesubgaleal mass surmounted by a foul smellingulcer overlying the posterior part of the ver-

tex. Neuroradiological studies confirmed a

large extracranial mass destroying the under-

lying bone and involving the extradural spacewith displacement but not occlusion of thesuperior sagittal sinus.A basal cell carcinoma (weight 675 gm)

was removed en bloc on 3 May 1991. Largeareas of dura mater were thus exposed bilat-erally with the intervening sagittal sinus. Allwere packed with BIPP. Post operatively shereceived 5500 cGY in 20 fractions over fourweeks with 4 MeV x rays.

In early July 1991 she gradually becameprogressively agitated and confused withintermittent bihemispheric signs. She eventu-ally lapsed into a coma. There was no mean-ingful neurological response in the limbs formany weeks but she maintained her vitalsigns and self ventilation. CT of the brainshowed diffuse cerebral oedema in both pari-eto-occipital lobes, more on the right side.

In December 1991 the BIPP pack wasremoved. She thereafter showed a progressivereturn to full alertness, rapport, cognition,and coordinated bodily activity.On 20 December CT showed complete

resolution of cerebral oedema but the appear-ance of patchy areas of high attenuation inthe right parieto-occipital cortex subjacent tothe exposed dura mater.The "ulcer" remained unsuitable for graft-

ing due to the presence of immature granula-tions, areas of slough, and a wide rim ofblackened devitalised bone. A large BIPPpack was reapplied in the hope of obtaining aclean granular bed for later grafting. After thisprocedure she again became progressivelyrestless, dysarthric, insomnolent, and con-fused. On 26 April 1992 she showed a rela-tively rapid deterioration in her consciouslevel and became unresponsive. The possibil-ity of bismuth toxicity was considered and theBIPP pack was again removed. Blood bis-muth concentration was 52 ng/l (April 1992).Her conscious level once more improved tonormal over a fortnight with the blood bis-muth concentration falling to 24 ng/l on 14May 1992. The idea of bismuthism was morecertain although she had never displayed typi-cal myoclonic jerks as described with oralingestion of bismuth salts on a long term basis.

Periodic CT showed abnormal features ofextensive cerebral oedema and high attenua-tion in the parieto-occipital cerebral cortex(fig 1). On MRI (axial and coronal scans) the

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Extradural application of bismuth iodoform paraffin paste causing relapsing bismuth encephalopathy

Figure 1 CT scanshowing extensive whitematter oedema causing amass effect and highattenuation of the parieto-occipital cerebral cortex(more on the right).

changes were more extensive both in TI andT2 images (fig 2). Recent CT showed evi-dence of cerebral atrophy but no evidence oftumour. The naked dura is currently coveredby a simple dressing of sofratulle andlyofoam. Her neurological state remains satis-factory.

DiscussionFatal poisoning (accidental ingestion or par-enteral injections) and mild toxicities such as

dermatitis, skin rashes, and allergic reactions(local application) are well recognised butinfrequent complications of bismuth treat-ment.5 Although brain damage by bismuthwas recorded as early as 1922 by Levaditi,6 ithas been refuted by some.7

In 1973, 29 cases of bismuth neurotoxicitywere reported in Australia.89 All recoveredafter discontinuing the drug. In France, 950cases of bismuth encephalopathy werereported; 70 were fatal.8 In both series oralpreparations of bismuth had been given forvarious bowel disorders. The neurologicalsyndromes were characterised by increasingconfusion, ataxia, and myoclonus.

Kruger et a15 suggested that bismuth bindswith the thiol group of enzymes in cerebralintracellular enzyme systems concerned withoxidative cerebral metabolism. Bismuthcrosses the blood-brain barrier and disturbsoxidative cerebral metabolism causingincreased lactate production, decreased con-

sumption of oxygen and glucose, and loweredcerebral blood flow.

Transient facial paralysis related to BIPPpacking was reported in 1985 in a 58 year oldCaucasian woman who had an infected mas-

toidectomy cavity and a benign aural polyp of

the facial ridge.3 Another case of neurotoxic-ity (reversible bismuth encephalopathy) wasreported in which a large BIPP pack was usedafter surgery for keratocyst of the mandible.Seven weeks later the patient presented withgeneral malaise, insomnia, and mildParkinsonian tremors with stiff arms. Theblood bismuth concentration was greater than30 ng/l. He recovered completely afterremoval of the BIPP pack.

In the case now reported, two separateinstances occurred where the manifestationsof neurotoxicity were progressive agitatedconfusion, insomnia, dysarthria, and thendeterioration in the level of consciousnessleading to coma. The patient recovered spon-taneously after removal of the BIPP pack onboth occasions. Her clinical state correlatedwell with the blood bismuth concentrationsduring the second episode. Although theblood bismuth concentrations were not esti-mated during the first episode of toxicencephalopathy the relapsing and remittingcourse of the disease correlated so well withthe BIPP application and discontinuation thata causal relation seems highly probable.The normal concentration of bismuth in

blood is between 1-5 ng/l.4 '° A safety value of30-50 ng/l and an alarm concentration of 100ng/l have been suggested in the past but noproof is available to support the choice ofthese concentrations.'0 According toSerfontein and Mekel," blood bismuth con-centrations do not seem to reflect bismuthconcentration in the brain. Blood bismuthmay return to normal but high concentrationsof intracerebral bismuth may still exist.

Escourolle et al2 have reported 12 post-mortem studies of bismuth poisoning afteroral ingestion. In these cases the concentra-tion of bismuth in the brain tissue was morethan 2 mg/kg, 100 to 1000 times higher thanin the normal brain. The concentration ofbismuth is highest in the grey matter espe-cially in the basal ganglia, cerebral cortex,and cerebellar cortex as well as in themeninges. Interestingly, in a fatal case of bis-muth encephalopathy described by Liessenset al"3 after oral ingestion of bismuth salt, theconcentration of bismuth in visceral organsand different parts of the CNS remained veryhigh despite a drastic decrease of blood bis-muth. They found histopathological evidenceof non-specific anoxic lesions including wide-spread loss of Purkinje cells in the cerebel-lum. The blood bismuth concentration of 52ng/l in our case where BIPP was appliedlocally over the dura mater was significant.There were no typical myoclonic seizures.These however, have only been reported inpatients who had bismuth blood concentra-tions ranging from 150 to 2200 ng/l."14 1

Findings from CT showing diffuse lowattenuation areas in the brain with patchyareas of increased attenuation in the basalganglia and the cerebral cortex have beenreported by Gardeur et al'5 in five cases of bis-muth encephalopathy after oral ingestion ofbismuth salts. The increased attenuation inthe grey matter contrasted with decreased

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Figure 2 MRI (axial views: Tl (A) and T2 (B) images) showing extensive cerebraloedema and hyperintense areas in the dura mater, central white matter (crumpled oliveappearance), and periventricular ependymal lining, more clearly visible on sequentialcoronal scans (C).

attenuation of the white matter, particularlyin the centrum semiovale of each hemisphere.Ventricular dilatation in three cases andincreased attenuation in the cerebellum inone case were also noted. Follow up CTstudies in one case showed regression ofabnormal findings. The regression accompa-nied the clinical improvement, which in everycase followed the termination of the bismuthintake.

The areas of increased attenuation seen inthe cerebral CT studies are most certainlyrelated to the high intracellular bismuth con-centration in the cerebral tissue. The highatomic number of bismuth (Z = 83) isresponsible for the increased attenuation val-ues.'5 The CT findings in our case charac-terised by diffuse areas of low attenuation inboth parieto-occipital regions subjacent to theBIPP pack were suggestive of cerebraloedema with mass effect and increased atten-uation in the dura mater and subjacent cortexsuggest local absorption of bismuth from theBIPP pack via the adjacent dura mater or itscirculation. MRI showed far more extensivecerebral oedema and peculiar stippled andcrumpled olive appearances in deep whitematter.

Although the role of bismuth in antisepsisrequires further clarification, there is clinicalevidence that BIPP is efficacious in the man-agement of postoperative surgical cavities. Italters the course of local recurrence ofchronic infections in ear, nose, and throat,dental, and neurosurgical practices, and pro-motes granulations. Bismuth encephalopathyis a major concern, however, that needs to beconsidered, particularly if long term applica-tion is likely to lesions in close proximity toneural tissue.

ConclusionsLong term extradural application of a largeBIPP pack may cause bismuth encephalopa-thy. Diffuse cerebral oedema subjacent to theBIPP pack and abnormal changes in the cere-bral cortex, deep white matter, and deepnuclear masses may be seen on CT and MRI(more pronounced with MRI). Blood bis-muth concentrations may be increased, corre-lating well with the clinical state. One suchcase is reported.

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Extradural application of bismuth iodoform paraffin paste causing relapsing bismuth encephalopathy

Close attention to neurological and psychi-atric symptoms is mandatory in anyonetreated long term by BIPP packings, particu-larly in those cases where packs are immedi-ately adjacent to neural tissue. Routineestimation of blood bismuth concentrationsin patients so treated may be appropriate.

We gratefully thank Mrs Ann Langford for the preparation ofthis manuscript, and Dr E W Jones and Dr N Powell, neuro-radiologists, for the CT and MRI studies. The patient wasoriginally admitted under the care of Mr P J E Wilson, for-merly consultant neurosurgeon at Morriston Hospital,Swansea. Blood bismuth concentrations were assayed by theMRC Heavy Metal Toxicity Unit, New Cross Hospital,London.

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