Peripheral neuropathy-an unusual complication of meningococcemia A case of meningococcemia with a persisting peripheral neuropathy and gangrene of the fingers is presented. These unusual complications are thought to be related to the diffuse intravascular cowgulation syndrome.
William D. Engber, M.D., Madison, Wis., Larry B. Marti, LTC, MC, USA, Washington, D. C., and Carroll T. Moore, M.D., Big Springs, Texas
Meningococcal disease, due to Neisseria meningitidis, is a generalized infection involving many systems. In addition to the central nervous system, it may involve the cardiac, pulmonary, renal, musculoskeletal, peripheral vascular, peripheral nervous, and dermatologic systems. We report a case of meningococcemia with subsequent peripheral neuropathy and gangrene of the fingers, and we review the literature concerning these complications.
Case history B. R., a 17-year-old Caucasian boy, was admitted to the hospital approximately 6 hours after the onset of fever, chills, sore throat, earache, and arthralgia involving the knees and ankles. The admitting diagnosis was acute upper respiratory tract infection, probably viral in origin. During the next 12 hours he developed nunc hal rigidity, an ecchymotic rash involving the extremities, trunk, and face, and acrocyanosis of the hands and feet. The spine fluid contained 15,300 white blood cells with 100% polymorphonuclears; the protein was 430 mg%; and glucose was 6 mg%, compared to blood glucose of 114 mg%. The working diagnosis was changed to meningococcemia with meningitis and diffuse intravascular coagulation. He was treated with intravenous aqueous penicillin and heparin. Cerebrospinal fluid cultures were positive for Neisseria meningitidis, serotype Bo.' Over the next several days there was a gradual improvement in the systemic symptoms, but it was apparent that considerable damage had occurred in both upper extremities. He had a partial low left median nerve palsy involving both sensory and motor components and a complete low right ulnar nerve palsy. There were residual ischemic changes in the left Received for publication Aug. 23, 1976. Revised for publication Feb. 23, 1977. Reprint requests: William D. Engber, M.D., Department of Surgery, University of Wisconsin Hospitals, 1300 University Ave., Madison, Wis. 53706.
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THE JOURNAL OF HAND SURGERY
hand with dry gangrene of the index and long finger distal to the proximal interphalangeal level. Other digits were affected less severely. Treatment included splinting of the hands, physical therapy to maintain range of motion, and whirlpool baths for gentle debridement. Necrotic areas on the left hand demarcated and were allowed to autoamputate except for the index and long fingers where two-stage amputations through the proximal interphalangeal joint were carried out some 3 months after the onset. Some improvement in the right ulnar and left median neuropathies first was noted during the third month. Appropriate splinting was continued, but despite the use of a short opponens splint, an adduction contracture of the left thumb developed. Six months after onset, a Z-plasty of the first cleft was done with a partial release of the adductor pollicis insertion. By 9 months even further neurologic recovery was evident. At this time weak voluntary activity of the abductor pollicis brevis muscle was demonstrable and some sensation had returned to the level of the bases of the index and long fingers. In the right hand, although there was weak intrinsic function, mild clawing remained. Due to this progressive improvement, further surgical treatment was deferred.
Discussion Neisseria meningitidis is a gram-negative, nonmotile coccus which usually is found in pairs. Systemic involvement generally results from spread of the organism from the nasopharynx to the blood. Constitutional symptoms of sepsis vary greatly in severity, but common features include fever, chills, myalgia, meningoencephalitis, and rash. Many reports have been written about meningococcal disease, but complications usually are mentioned only in passing. l . a Everett 4 has tabulated complications and residuals in 67 cases of meningococcal disease in a military population. Peripheral neuropathy is a rare complication. Wolf and Birbara5 reported "temporary paresis of peripheral
September, 1977
Vol. 2, No.5, pp. 404-405
Vol. 2 No.5 September, 1977
and motor nerves" in two patients. In one patient, the median and ulnar nerves were involved; and in the other, the axillary, radial, musculocutaneous, long thoracic, median, and ulnar nerves were affected. Levin and Painter6 noted a "transient neuritis," predominantly of the lower extremities, in six patients. No reports of a persisting peripheral neuropathy, as was seen in this patient, have been found. Loss of skin in areas of ecchymosis and in the digits also is an unusual complication of meningococcemia. Wolf and Birbara noted three cases of ischemic necrosis in ecchymotic areas in 112 patients; and Stiehm and Damrosch 7 reported one case of "severe skin slough" in their 51 cases. McGehee, Rapaport, and Hjort 8 reported one case of skin necrosis and one case of gangrene of a distal phalanx in 19 patients. Injury to the vascular endothelium, probably endotoxic in origin, may precipitate a hypercoagulable state followed by diffuse intravascular coagulation, with consumption of clotting factors and hemorrhagic manifestations. This has been termed consumptive coagulopathy or diffuse intravscular coagulation syndrome. It has been shown to occur in certain patients with severe meningococcal sepsis8 and is the most likely cause for the peripheral neuropathy and gangrene seen in the patient in this report. Although the mechanism of intravascular clotting in meningococcemia remains unproven, the most prevalent opinion has been that endotoxic damage to the endothelium is the initiating factor. 8, 9 An alternative consideration 1 is the possibility that shock itself, endotoxic in origin, is the mediator of endothelial damage, precipitating the coagulation process. Whether shock causes or results from intravascular coagulation or is in any way related remains unclear. Once the clotting process within vessels is initiated, there follows a reduction in serum fibrinogen, prothrobin, factors V and VII, and platelets. Secondary fibrinolysis may occur, resulting in fibrin split products demonstrable in the serum. Disseminated fibrin thrombi in small vessels of many organ systems, resulting in local tissue necrosis, is the characteristic histologic finding in this disorder. 8 The frequency of occurrence of consumption coagu-
Meningococcemia with peripheral neuropathy
405
lopathy in meningococcemia remains unclear. McGehee, Rapaport, and Hjort correlated its presence with endotoxic shock and a much higher mortality ratefive of six patients with evidence of consumptive coagulopathy died whereas only one of 13 patients without evidence of consumptive coagulopathy died. Its potential occurrence certainly justifies diagnostic studies such as fibrinogen level, fibrin split products, and platelet count whenever a diagnosis of acute meningococcemia is made or is considered seriously. Laboratory confirmation of consumptive coagulopathy secondary to meningococcemia justifies a trial period of heparin therapy. 1 Some series 8 , 10 have reported good responses; but others have been less favorable. If heparin is of value, it is only one adjunct in the complex management of these seriously ill patients. REFERENCES 1. Bell WE, Silbert DL: Meningococcal meningitis: Past and present concepts. Milit Med 136:601-61 1,1971 2. Varela GE, Gilmore GD: Meningococcal disease outbreak at Fort Leonard Wood, Missouri. Milit Med 136:723-727, 1971 3. Kaufman B, Levy H, Zaleznak BD, et al; Statistical analysis of 242 cases of meningococcus meningitis. Pediatr 38:705-716, 1951 4. Everett ED: Complications and residuals of meningococcal disease. Milit Med 136:612-616, 1971 5. Wolf RE, Birbara CA: Meningococcal infections at an army training center. Am J Med 44:243-255, 1968 6. Levin S, Painter MB: The treatment of acute meningococcal infection in adults. Ann Intern Med 64: 10491065, 1966 7. Stiehm ER, Damrosch DS: Factors in the prognosis of meningococcal infections. Pediatr 68:457-467, 1966 8. McGehee WG, Rapaport SI, Hjort PF: Intravascular coagulation in fulminant meningococcemia. Ann Intern Med 67:250-260, 1967 9. Evans RW, Glick B, Kimball F, et al: Fatal intravascular consumption coagulopathy in meningococcal sepsis. Am J Med 46:910-918, 1967 10. Abildgaard CF, Corrigan 11, Seeler RA, et al: Meningococcemia associated with intravascular coagulation. Pediatrics 40:78-82, 1967
William D. Engber, M.D., Madison, Wis., Larry B. Marti, LTC, MC, USA, Washington, D. C., and Carroll T. Moore, M.D., Big Springs, Texas
Meningococcal disease, due to Neisseria meningitidis, is a generalized infection involving many systems. In addition to the central nervous system, it may involve the cardiac, pulmonary, renal, musculoskeletal, peripheral vascular, peripheral nervous, and dermatologic systems. We report a case of meningococcemia with subsequent peripheral neuropathy and gangrene of the fingers, and we review the literature concerning these complications.
Case history B. R., a 17-year-old Caucasian boy, was admitted to the hospital approximately 6 hours after the onset of fever, chills, sore throat, earache, and arthralgia involving the knees and ankles. The admitting diagnosis was acute upper respiratory tract infection, probably viral in origin. During the next 12 hours he developed nunc hal rigidity, an ecchymotic rash involving the extremities, trunk, and face, and acrocyanosis of the hands and feet. The spine fluid contained 15,300 white blood cells with 100% polymorphonuclears; the protein was 430 mg%; and glucose was 6 mg%, compared to blood glucose of 114 mg%. The working diagnosis was changed to meningococcemia with meningitis and diffuse intravascular coagulation. He was treated with intravenous aqueous penicillin and heparin. Cerebrospinal fluid cultures were positive for Neisseria meningitidis, serotype Bo.' Over the next several days there was a gradual improvement in the systemic symptoms, but it was apparent that considerable damage had occurred in both upper extremities. He had a partial low left median nerve palsy involving both sensory and motor components and a complete low right ulnar nerve palsy. There were residual ischemic changes in the left Received for publication Aug. 23, 1976. Revised for publication Feb. 23, 1977. Reprint requests: William D. Engber, M.D., Department of Surgery, University of Wisconsin Hospitals, 1300 University Ave., Madison, Wis. 53706.
404
THE JOURNAL OF HAND SURGERY
hand with dry gangrene of the index and long finger distal to the proximal interphalangeal level. Other digits were affected less severely. Treatment included splinting of the hands, physical therapy to maintain range of motion, and whirlpool baths for gentle debridement. Necrotic areas on the left hand demarcated and were allowed to autoamputate except for the index and long fingers where two-stage amputations through the proximal interphalangeal joint were carried out some 3 months after the onset. Some improvement in the right ulnar and left median neuropathies first was noted during the third month. Appropriate splinting was continued, but despite the use of a short opponens splint, an adduction contracture of the left thumb developed. Six months after onset, a Z-plasty of the first cleft was done with a partial release of the adductor pollicis insertion. By 9 months even further neurologic recovery was evident. At this time weak voluntary activity of the abductor pollicis brevis muscle was demonstrable and some sensation had returned to the level of the bases of the index and long fingers. In the right hand, although there was weak intrinsic function, mild clawing remained. Due to this progressive improvement, further surgical treatment was deferred.
Discussion Neisseria meningitidis is a gram-negative, nonmotile coccus which usually is found in pairs. Systemic involvement generally results from spread of the organism from the nasopharynx to the blood. Constitutional symptoms of sepsis vary greatly in severity, but common features include fever, chills, myalgia, meningoencephalitis, and rash. Many reports have been written about meningococcal disease, but complications usually are mentioned only in passing. l . a Everett 4 has tabulated complications and residuals in 67 cases of meningococcal disease in a military population. Peripheral neuropathy is a rare complication. Wolf and Birbara5 reported "temporary paresis of peripheral
September, 1977
Vol. 2, No.5, pp. 404-405
Vol. 2 No.5 September, 1977
and motor nerves" in two patients. In one patient, the median and ulnar nerves were involved; and in the other, the axillary, radial, musculocutaneous, long thoracic, median, and ulnar nerves were affected. Levin and Painter6 noted a "transient neuritis," predominantly of the lower extremities, in six patients. No reports of a persisting peripheral neuropathy, as was seen in this patient, have been found. Loss of skin in areas of ecchymosis and in the digits also is an unusual complication of meningococcemia. Wolf and Birbara noted three cases of ischemic necrosis in ecchymotic areas in 112 patients; and Stiehm and Damrosch 7 reported one case of "severe skin slough" in their 51 cases. McGehee, Rapaport, and Hjort 8 reported one case of skin necrosis and one case of gangrene of a distal phalanx in 19 patients. Injury to the vascular endothelium, probably endotoxic in origin, may precipitate a hypercoagulable state followed by diffuse intravascular coagulation, with consumption of clotting factors and hemorrhagic manifestations. This has been termed consumptive coagulopathy or diffuse intravscular coagulation syndrome. It has been shown to occur in certain patients with severe meningococcal sepsis8 and is the most likely cause for the peripheral neuropathy and gangrene seen in the patient in this report. Although the mechanism of intravascular clotting in meningococcemia remains unproven, the most prevalent opinion has been that endotoxic damage to the endothelium is the initiating factor. 8, 9 An alternative consideration 1 is the possibility that shock itself, endotoxic in origin, is the mediator of endothelial damage, precipitating the coagulation process. Whether shock causes or results from intravascular coagulation or is in any way related remains unclear. Once the clotting process within vessels is initiated, there follows a reduction in serum fibrinogen, prothrobin, factors V and VII, and platelets. Secondary fibrinolysis may occur, resulting in fibrin split products demonstrable in the serum. Disseminated fibrin thrombi in small vessels of many organ systems, resulting in local tissue necrosis, is the characteristic histologic finding in this disorder. 8 The frequency of occurrence of consumption coagu-
Meningococcemia with peripheral neuropathy
405
lopathy in meningococcemia remains unclear. McGehee, Rapaport, and Hjort correlated its presence with endotoxic shock and a much higher mortality ratefive of six patients with evidence of consumptive coagulopathy died whereas only one of 13 patients without evidence of consumptive coagulopathy died. Its potential occurrence certainly justifies diagnostic studies such as fibrinogen level, fibrin split products, and platelet count whenever a diagnosis of acute meningococcemia is made or is considered seriously. Laboratory confirmation of consumptive coagulopathy secondary to meningococcemia justifies a trial period of heparin therapy. 1 Some series 8 , 10 have reported good responses; but others have been less favorable. If heparin is of value, it is only one adjunct in the complex management of these seriously ill patients. REFERENCES 1. Bell WE, Silbert DL: Meningococcal meningitis: Past and present concepts. Milit Med 136:601-61 1,1971 2. Varela GE, Gilmore GD: Meningococcal disease outbreak at Fort Leonard Wood, Missouri. Milit Med 136:723-727, 1971 3. Kaufman B, Levy H, Zaleznak BD, et al; Statistical analysis of 242 cases of meningococcus meningitis. Pediatr 38:705-716, 1951 4. Everett ED: Complications and residuals of meningococcal disease. Milit Med 136:612-616, 1971 5. Wolf RE, Birbara CA: Meningococcal infections at an army training center. Am J Med 44:243-255, 1968 6. Levin S, Painter MB: The treatment of acute meningococcal infection in adults. Ann Intern Med 64: 10491065, 1966 7. Stiehm ER, Damrosch DS: Factors in the prognosis of meningococcal infections. Pediatr 68:457-467, 1966 8. McGehee WG, Rapaport SI, Hjort PF: Intravascular coagulation in fulminant meningococcemia. Ann Intern Med 67:250-260, 1967 9. Evans RW, Glick B, Kimball F, et al: Fatal intravascular consumption coagulopathy in meningococcal sepsis. Am J Med 46:910-918, 1967 10. Abildgaard CF, Corrigan 11, Seeler RA, et al: Meningococcemia associated with intravascular coagulation. Pediatrics 40:78-82, 1967
