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multiple myeloma ( mm ) is a human b - cell neoplasm characterized by the clonal expansion of malignant plasma cells in the bone marrow .
the cause of this disease is only partially understood , but the production of soluble factors by the myeloma cells is likely to be involved .
the most important complications are hypercalcemia associated with rapid skeletal dissolution , acute or chronic renal insufficiency , and infection .
all these , along with less common complications such as the hyperviscosity syndrome , hyperuricemia , and neurologic involvement , must be recognized and managed appropriately to achieve optimal results from primary therapy .
the serum hyperviscosity syndrome has been described clinically as the triad of bleeding , visual signs and symptoms , and neurologic manifestations ( 1 , 2 ) .
this oncologic emergency occurs in patients with igm , igg , and iga monoclonal gammopathies as well as in some patients with polyclonal immunoglobulin disorders ( 3 ) .
we reported a patient with hyperviscosity - induced cerebral infarction as the first sign of igg multiple myeloma based on clinical , laboratory , brain mri , and bone marrow biopsy .
a 68-yr - old right - handed woman was admitted to chonnam national university hospital on 6 march , 2002 due to hypesthesia and monoplegia in the left leg .
other neurological examinations were normal except monoplegia , hypesthesia , increased deep tendon reflex ( 3 + ) with ankle jerks , and up - going babinski in the left leg .
diffusion- and t2-weighted mri revealed a hyperintense lesion in the callosomarginal territory of the right anterior cerebral artery , and mr angiography did not show significant stenosis on the intra- and extracranial artery ( fig .
laboratory data were as follows : hematocrit 26.6% ( normal , 37 - 52 ) , hemoglobin 8.2 g / dl ( normal , 12 - 18 ) , erythrocyte sedimentation rate 127 mm / hr ( normal , below 20 ) , leukocyte 4.610/l ( normal , 4.3 - 10.8 ) and platelet counts 19010/l ( normal , 130 - 400 ) .
the prothrombin time was 80.8% ( 13.3/80.8/1.13 ; sec/%/inr ) of that of control ; partial thromboplastin time was 27.1 sec ( normal , 26.5 - 41 ) . the plasma level of protein c and s activity were in the normal range .
serum creatinine was 0.6 mg / dl ( normal , 0.6 - 1.5 ) , serum sodium 137 meq / l ( normal , 135 - 153 ) , potassium 4.1 meq / l ( normal , 3 - 5 ) , total calcium 7.1 mg / dl ( normal , 8.6 - 10.6 ) , ionized calcium 2.4
meq / l ( normal , 2.0 - 2.4 ) , and uric acid 1.5 mg / dl ( normal , 2.4 - 7 ) .
the total serum protein concentration was 9.6 g / dl ( normal , 6.0 - 8.0 ) , albumin was 1.8 g / dl ( normal , 3.5 - 5.5 ) , and globulins were 7.8 g / dl .
serum protein electrophoresis ( spep ) revealed hyperproteinemia , hypoalbuminemia and a prominent spike at the gamma - globulin region ( fig .
2 ) . levels of immuno - globunins were as follows : igg 6,060 mg / dl ( normal , 700 - 1,600 ) , iga 23.1 mg / dl ( normal , 70 - 400 ) , igm 55.4 mg / dl ( normal , 40 - 230 ) , ige 17.8 mg / dl ( normal , 0.0 - 100 ) and 2-microglobulin 1.08 mg / l ( normal , 0.7 - 3.4 ) .
her relative serum viscosity at 37 was 5.2 ( normal , 1.4 to 1.8 ) .
random urine protein was 23 mg / dl ( normal , 1.0 - 14.0 ) , but bence - jones protein was negative in urine .
roentgenograms revealed multiple lytic lesions of the skull and right 6th rib , and compression fracture of 9th thoracic vertebrae body .
she was treated by chemotherapy ( cyclophosphamide 200 mg / m per day ) with steroid pulse and then prednisone ( 70 mg / day ) for 5 days , where and she remained on intermittent chemotherapy .
every four weeks , routine blood tests and levels of immunoglobulins were performed . at 3 months ,
there was no recurrence of hyperviscosity syndrome or stroke during the follow - up of 25 months .
the typical features of multiple myeloma include bone pain , weakness , fatigue , fever and infection .
neurologic symptoms occur in a minority of patients with multiple myeloma : hypercalcemia may produce lethargy , weakness , depression , and confusion ; bony damage and collapse may lead to spinal cord compression , radicular pain , and loss of bowel and bladder control ; a bulky cranial multiple myeloma invading cerebrum may result in quadriparesis and headache ( 4 ) ; infiltration of peripheral nerves by amyloid can be a cause of carpal tunnel syndrome and other sensorimotor mono- and polyneuropathies ; hyperviscosity may lead to headache , fatigue , visual disturbances , retinopathy , dementia ( 5 , 6 ) , and cerebral infarction ( 7 , 8) . however , one bears in mind that multiple myeloma may be present with a neurological disease .
hyperviscosity is defined on the basis of the relative viscosity of serum as compared with water . whereas normal relative serum viscosity is 1.8 ,
symptoms of hyerviscosity occur at a level of 5 to 6 , a level usually reached at paraprotein concentrations of approximately 40 g / l for igm , 50 g / l for igg3 , and 70
hyperviscosity occurs relatively infrequently in patients with multiple myeloma , but one study reported an incidence of 4.2% among patients with igg protein ( 10 ) .
its occurrence has been ascribed to the presence in the serum of high molecular weight polymers of the igg proteins . in our case ,
major neurologic deficits occur in more than 25% of patients with myeloma and hyperviscosity syndrome ( 10 - 12 ) .
lethargy , hemiparesis , seizures , coma , and acute confusional states are most frequently cited .
we reported a 68-yr - old patient who developed monoplegia of the left leg as the first manifestation of multiple myeloma with hyperviscosity .
this case was rare in that it involved plasma cell leukemia with cerebral infarction associated with serum hyperviscosity .
we searched for cases of multiple myeloma with hyperviscosity presenting with cerebral infarction , and found only 2 reports ( 13 , 14 ) .
clinical conditions in which this possible role of hyperviscosity in cerebral infarction could be demonstrated have not been reported so far . in another reported cases of cerebral infarction in multiple myeloma ,
our case had no significant atherosclerotic lesion on intra- and extracranial vessels , and no risk factors of stroke except old age .
therefore , we suggest that hyperviscosity plays a key role in the pathogenesis of stroke in her with multiple myeloma , our case then , is consistent with the hypothesis that chronic blood hyperviscosity antedates the onset of symptomatic cerebrovascular disease .
thus , in patients with multiple myeloma , the monitoring of plasma viscosity was of major importance in order to evaluate the risk of cerebral infarction and decide the management for the prevention of stroke .
we believe that our patient represents a rare case of igg multiple myeloma associated with blood hyperviscosity and cerebral infarction .
based on our case study , and a review of the literature , we suggest that markedly elevated level of serum globulin in a patient with cerebral infarction requires measurement of blood viscosity , especially in patients with multiple myeloma .
cerebral infarction is an uncommon complication in multiple myeloma with hyperviscosity . 
 serum hyperviscosity may cause a variety of clinical manifestations including bleeding from mucosal membranes , congestive heart failure , retinopathy , and various neurologic deficits . 
 these manifestations have been attributed to the presence of large quantities of asymmetrical molecules of high molecular weight in the serum . 
 we recently experienced a case of multiple myeloma with acute cerebral infarction , which caused by hyperviscosity , as an initial manifestation in igg multiple myeloma , and reviewed the relevant literature of myeloma presenting with the stroke . 
 a 68-yr - old woman abruptly developed hypesthesia and monoplegia in the left leg . 
 the stroke confirmed by the brain mri and mr angiography , which revealed acute infarction at the right anterior cerebral artery territory . on admission , routine blood tests showed a slight decrease in hemoglobin and a marked increase in erythrocyte sedimentation rate . 
 peripheral blood smear , serum protein electrophoresis , serum visocity , and bone marrow aspiration showed that she had igg multiple myeloma with hyperviscosity . 
 she was treated by chemotherapy with cyclophosphamide and discharged with the improved clinical condition .