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Phycomycosis (Mucormycosis) of the Central Nervous System

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Phycomycosis (Mucormycosis) of the Central Nervous System Phycomycosis (Mucormycosis) of the Central Nervous System Report of a Case* DAVID L. REEVES, M.D., t DELBERT R. DICKSON, 5~.D., AND E. L. BENJAMIN, M.D. Santa Barbara, California Mucormycosis is a fungus infection character- tract. Mycosis has also occurred in tile eyes, cen- ized by the proliferation in tissue of broad, tral nervous system, lungs, gastrointestinal tract, branching, rarely septate hyphae. Species of the and subcutaneous lissues. In susceptible in- genera mucor, rhizopus, absidia, Mortierella, dividuals the organism propagates in a unique and basidiobolus, all of the class phycomycetes, manner, invading and proliferating within the have been observed as pathogens in the relatively muscular walls of arteries, and to a lesser extent few cases reported in which cultures have been veins and lymphatics, giving rise to purulent obtained? For this reason the now generally ac- arteritis, thrombosis, and consequent infarction. cepted term "phycomycosis" was suggested by Phycomycosis of the orbit and central nervous Lie and his co-workers 7 as a more appropriate system begins in the para-nasal sinuses and designation for this group of infections, in which spreads along vascular channels, leading to orbital sections of tissue reveal a fungus of the phyco- and cerebral complications by producing throm- mycete morphology. boarteritis of the branches of tile ophthalmic and These fungi are ubiquitous molds in nature, internal carotid arteries. Only 6 survivors of common as laboratory and household contami- cerebral phycomycosis have been reported and nants, and not ordinarily considered pathogenic. all of these individuals had residual neurologic Ultimate diagnosis depends on the hisLopaflm- deficits2 logic demonstration of the characteristic hyphae invading tissue and cannot be based solely on the Case Report isolation by culture of such saprophytic organ- History. A 30-year-old woman who had recognized isms. On the other hand, culture is necessary to diabetes mellitus for the last 6 years experienced epi- establish the toxonomic status of the etiologic sodes of nausea and vomiting on January 14, 1951. agent. Phycomycosis of the orbit and central These were followed by soreness of the throat and the following morning by confusion. She had been taking nervous system is generally caused by species of 30 units of insulin daily. The diabetes, which was mucor, rhizopus, or absidia. 4 thought at first to be the cause of her trouble, was found Phycomycosis appears to be on the increase. to be under control. Because of her sore throat, it was Prior to 1948 only 30 cases were collected from believed she was suffering from an upper respiratory the literature, 4 involving the central nervous infection. system. 5 In a comprehensive review, Straatsma Within a few days her confusion cleared. However, and his co-workers t~ reported 158 cases in the 19 she became drowsy and showed impaired movements of years from 1943 to 196~. One third of these in- the left eye, particularly on lateral gaze with weakness volved the nasal and paranasal sinuses, orbit, and of the left side of tile face and left arm. The spinal fluid pressure was normal and there were only 12 white cells central nervous system. The infection is prin- in the spinal fluid. On one occasion the blood leukocyte cipally a complication of other diseases, of which count was 37,000 and on another, 24,000. Blood cul- diabetes is the inost common, s In a recent series tures taken prior to her hospitalization were negative. A 4e per cent of the patients were diabetic. Other mild sinusitis was observed on the roentgenographic predisposing situations are leukemia, depression films. There had been no headache. of bone marrow, and generalized malignancy. As Examination. Because of the development of coma, with other mycoses, increased incidence in recent she was referred by her personal physician for hospitali- years seems related to the therapy with antibi- zation and diagnostic study on January ~0th. The otics, steroids, or antimetabolites. history was obtained from her husband and her physi- The portal of entry is usually a superficial lesion cian. Except for her pallor and colnatosc state, a slight injection of the nasopharynx was the only general phys- of the mucous membrane of the nose, paranasal ical abnormality found. There was startling pallor of sinuses, bronchopulmonary tree, or alimentary the optic fundi, as though the vessels had been obliter- ated or drained of their blood. An ophtbahnological consultant interprctcd this as indicative of complete Received for publication July 2, 1964. obstruction of both central retinal arteries, possibly due * Presented at the 10th annual meeting of the West- to an embolus. There was a left external rectus paresis. ern Neurosurgical Society, San Francisco, California, Babinski's sign was positive bilaterally and the abdomi- on October ~21, 1964. nal and epigastric reflexes were absent. She had little t Address: 316 West Junipero St., Santa Barbara, movement of the right arm and leg. California. Medical consultation led to the impression of a prob- 8~ Phycomycosis of Central Nervous System 83 FIG. 1. Broad branching nonseptate hyphae pro- Fro. 2. Note the pinching of the hypha as it pene- ]iferating within the wall of an ophthalmic artery and trates the thickened internal elastic lamella. Hotchkiss- into the septic thrombus with the arterial lumen. McManus, X 1100. H. & E., )<ll00. able infection of the respiratory tract. The diabetes was destroying the endothelium, and initiating a purulent under control so that the coma could not be attributed inflammatory response with subsequent thrombosis to that condition. A viral infection leading to encephal- (Figs. 1 and 2). The fungus was identified as phyeo- itis with the secondary development of a thrombotic pro- mycete by the staff of the Armed Forces Institute of cess was thought to be unlikely because of the elevated Pathology (AFIP Ace. 694863). ix leukocyte count. The white blood cells were not leuke- mia and showed simply a prominent left shift of the Discussion neutrophils. The cardiac picture did not suggest an embolic process. Awareness of the clinical features of mucormy- Course. She remained deeply comatose. Because of a cosis of the central nervous system can lead to its suspected septic process, she was given substantial diagnosis and treatment. ~,s,9 The possibility amounts of antibiotics. On the day of her death necrosis should be borne in mind in patients with de- of the lids of the left eye was noted, as well as destruc- bilitating disease, in those receiving antibiotics, tion of the globe of the left eye and collapse of its an- steroids, or antimetabolic agents, and particularly terior chamber. The necrosis involved all the soft tissues of the orbit and extended to the lateral aspect of the in those with diabetic acidosis. Even with an bridge of the nose. It was believed this represented a aroused clinical suspicion, in a diabetic patient retrograde thrombosis of the ophthalmic artery bilat- with symptoms of sinusitis, orbital cellulitis, erally. She died ~ days after admission. ophthalmoplegia, and neurological abnormalities Post-mortem Findings. The gross anatomic findings suggestive of meningoencephalitis, the progres- were basilar fibrinopurulent leptomeningitis with bi- sion of the disease is often so rapid that institu- lateral cavernous sinus thrombosis, as well as throm- tion of fungicidal therapy at this time may not boses of the left anterior and middle cerebral arteries, lead to recovery; or recovery, if achieved, would the intracranial portion of the left internal carotid be at the expense of disabling sequelae. Ampho- artery, and both ophthalmic arteries. There was also an tericin B is the most effective therapeutic agent acute suppurative left otitis media, suppurative eth- moiditis, suppurative sphenoiditis, plus bilateral cellu- and the prognosis which had been uniformly dis- litis of the orbits, retro-orbital tissues and periorbital couraging has at least brightened with its use. 2,3 skin. No other visceral lesions were encountered. Bac- The importance of establishing the diagnosis and teriologic cultures of material obtained from the carrying out early treatment is clear. It might necropsy were inconclusive. Fungus cultures were not even seem wise to begin treatment on the basis of taken. clinical findings without prior verification by cul- Microsections of the thrombosed vessels revealed ture. massive proliferation of large nonseptate branching Smith and Kirchner TM have emphasized the hyphae, which st,-..ined clearly with hcmatoxylin and diagnostic value of the presence of a black nasal less intensely with the periodic acid-Schiff reaction and the methenamine silver method. A striking picture was turbinate in nasal phycomycosis. Biopsy of ac- produced by the profuse proliferation of the hyphae cessible lesions such as those occurring in the beneath the endothelium and the internal elastic lamella nasal mucosa or skin produces conclusive evi- of arteries, lifting these structures from the media, dence. .
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