Lymphomatoid Granulomatosis Clinically Confined to the CNS A Case Emre
Report
Kokmen, MD; James K. Billman, Jr, MD; Murray R. Abell, MD, PhD
\s=b\ A 38-year-old man developed pain and peripheral-type weakness on the right side of his face and was discovered to have decreased hearing bilaterally, as well as optic nerve swelling on the right. The pain and optic nerve swelling subsided over a period of six weeks, but hearing loss and facial weakness persisted. Thirty months later, he developed
dysphagia, ataxia, dysarthria, nystagmus, and progressive spastic quadriparesis. He died approximately four years after the onset of the illness. Although no evidence of disease was found other than in the central nervous system during life, two nodules in the right lower lung were found on autopsy. The examination of these nodules, as well as the brain stem, showed an angiocentric and angionecrotic process with lymphoreticular and plasmacytoid invasion. (Arch Neurol 34:782-784, 1977)
Liebow
et al1 defined
lymphomagranulomatosis as an angiocentric and angiodestructive proliferative lymphoreticular and granulomatous disease involving pre¬ dominantly the lungs. Nervous system toid
involvement occurred in at least 20% of their patients.1Accepted
for publication April 25, 1977. From the Departments of Neurology (Dr Kokmen) and Pathology (Drs Billman and Abell), University of Michigan Medical School, Ann Arbor. Reprint requests to Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109 (Dr Kokmen).
The following case emphasizes that the disease can manifest itself exclu¬ sively by neurologic signs and symp¬ toms.
REPORT OF A CASE
38-year-old illiterate construction worker was hospitalized during December 1970. He reported pain in the right side of the face and "pink eye" for 12 days. An ulcer of the right cornea had been discov¬ ered two days before admission, and a foreign object was removed. Soon after¬ wards, weakness of the right side of his face developed. He also reported decreased hearing for three years. Examination disclosed fluid behind the right tympanic membrane, mild conjunc¬ tivitis on the right, and a right peripheral facial weakness with diminished taste perception on the anterior two thirds of the tongue. The right optic disk was elevated and swollen. Visual acuity was 20/80 on the right and 20/100 on the left. Visual fields were full to confrontation. Extraocular movements were normal, as were corneal reflexes and sensation of the face. There was marked bilateral hearing loss by audiometry. Caloric stimulation showed diminished response to ice water in the right ear and no response in the left. Sensory, motor, and reflex examination of the extremities gave normal results. The patient was oriented but had difficulty with arithmetic. Electromyography dem¬ onstrated fibrillation potentials in the right frontalis, zygomaticus, and orbicularis oculi muscles. The right facial nerve could not be stimulated. ElectroencephaloA
Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/13/2015
was mildly abnormal with excessive diffuse and shifting minor theta bursts. Skull x-ray films were normal. Chest roentgenogram showed right apical pleural scar¬ ring. A right internal carotid arteriogram was normal. Cerebrospinal fluid contained one RBC and four WBCs per cubic milli¬
gram
meter; protein, 59 mg/100 ml; glucose, 52 mg/100 ml, with a concurrent blood glucose level of 60 mg/100 ml. There was no growth of bacteria, fungi, or mycobacteria. Colloi¬ dal gold and VDRL tests were negative. An isotopie brain scan was normal. Serum
protein electrophoresis disclosed the fol¬ lowing values: total protein, 7.6 gm/100 ml; albumin, 47.6%; ,-globulin, 23.3%. By
radial immunodiffusion IgA was 395 mg/ 100 ml (normal, 40 to 364); IgM, 230 mg/100 ml (normal, 10 to 270); and IgG, 2,000 mg/ 100 ml (normal, 660 to 1,700). Hemogram and erythrocyte sedimentation rate were normal. Latex rheumatoid arthritic factor was positive at a titer of 1:160, cold agglutinin titer was 1:80, and antinuclear anti¬ body was negative. A culture from the right middle ear showed coagulase-negative staphylococci. Candida and Trichophyton skin tests showed positive delayed hypersensitivity. Prednisone therapy, 60 mg/day, was initiated. Optic nerve swell¬ ing diminished in 17 days and the patient was discharged on the 49th hospital day. Prednisone administration was discontin¬ ued after two months. Three years later, he was readmitted with complaints of difficulty walking, talk¬ ing, and swallowing and an 11.4-kg weight loss over the preceding four months. The patient was alert; his speech was unintelli¬ gible. He responded to simple commands
Fig 1.—Transverse section hyde-fixed cerebellum has
of formalde¬ infiltration of white matter and dentate nuclei by lymphomatoid granulomatosis. Central pons is also involved (x 1).
and identified
pointing
some
objects correctly by
at them.
Visual fields were normal to confrontation by finger motion. The right pupil was larger than the left, and ptosis was present on the right. There was unsustained slow nystagmus of the abducting eye when right horizontal gaze was attempted; otherwise, lateral eye movements were absent and there was marked limitation of upward and down¬ ward gaze. There was bilateral hearing loss and complete right-sided, peripheral facial weakness. Functions of other cranial nerves were normal. Generalized muscle weakness was pres¬ ent in all extremities, somewhat greater on the left. Tone was generally increased. There were fasciculations in the right thigh. Muscle stretch reflexes were hyper¬ active and symmetrical; the plantar re¬ flexes were bilaterally extensor. Electro¬ myography showed 3+ fibrillations, posi¬ tive waves, and fasciculations in all four extremities. Motor nerve conduction veloci¬ ties were normal. An electroencephalo¬ gram was again mildly abnormal. A right internal carotid and left vertebral arteriography and an isotopie brain scan were normal. Pneumoencephalogram showed mild dilation of all ventricles, and very little air was seen over the convexity. The first cerebrospinal fluid specimen was obtained before instillation of air. No RBCs and three mononuclear WBCs were detected. Other values were as follows: glucose, 57 mg/100 ml; protein, 47 mg/100 ml; IgG, 6.4 mg/100 ml; albumin, 16.5 mg/ 100 ml; IgG-albumin ratio; 1:2.6. No growth occurred in cultures. A second cerebro¬ spinal fluid evaluation five days later disclosed seven RBCs and three WBCs; protein, 53 mg/100 ml; and glucose, 51 mg/ 100 ml. IgG level was 8.4 mg/100 ml, and albumin concentration was 14 mg/100 ml with a ratio of 1:1.7. VDRL test was nega¬ tive. Anaerobic culture yielded Propioni-
Fig 2.—Destructive lesion of central pons with loss of myelinated tracts Atypical lymphoreticular cells cuff vessels (Luxol fast blue, 200). bacterium
acnes.
Chest roentgenogram
unchanged from that obtained during the first hospitalization. Admission labora¬ was
tory studies disclosed
a low serum potas¬ sium level, which improved during hospi¬ talization. Serum protein electrophoresis showed the following values: total protein, 7.7 gm/100 ml, with albumin, 42.8%,
Report
Kokmen, MD; James K. Billman, Jr, MD; Murray R. Abell, MD, PhD
\s=b\ A 38-year-old man developed pain and peripheral-type weakness on the right side of his face and was discovered to have decreased hearing bilaterally, as well as optic nerve swelling on the right. The pain and optic nerve swelling subsided over a period of six weeks, but hearing loss and facial weakness persisted. Thirty months later, he developed
dysphagia, ataxia, dysarthria, nystagmus, and progressive spastic quadriparesis. He died approximately four years after the onset of the illness. Although no evidence of disease was found other than in the central nervous system during life, two nodules in the right lower lung were found on autopsy. The examination of these nodules, as well as the brain stem, showed an angiocentric and angionecrotic process with lymphoreticular and plasmacytoid invasion. (Arch Neurol 34:782-784, 1977)
Liebow
et al1 defined
lymphomagranulomatosis as an angiocentric and angiodestructive proliferative lymphoreticular and granulomatous disease involving pre¬ dominantly the lungs. Nervous system toid
involvement occurred in at least 20% of their patients.1Accepted
for publication April 25, 1977. From the Departments of Neurology (Dr Kokmen) and Pathology (Drs Billman and Abell), University of Michigan Medical School, Ann Arbor. Reprint requests to Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109 (Dr Kokmen).
The following case emphasizes that the disease can manifest itself exclu¬ sively by neurologic signs and symp¬ toms.
REPORT OF A CASE
38-year-old illiterate construction worker was hospitalized during December 1970. He reported pain in the right side of the face and "pink eye" for 12 days. An ulcer of the right cornea had been discov¬ ered two days before admission, and a foreign object was removed. Soon after¬ wards, weakness of the right side of his face developed. He also reported decreased hearing for three years. Examination disclosed fluid behind the right tympanic membrane, mild conjunc¬ tivitis on the right, and a right peripheral facial weakness with diminished taste perception on the anterior two thirds of the tongue. The right optic disk was elevated and swollen. Visual acuity was 20/80 on the right and 20/100 on the left. Visual fields were full to confrontation. Extraocular movements were normal, as were corneal reflexes and sensation of the face. There was marked bilateral hearing loss by audiometry. Caloric stimulation showed diminished response to ice water in the right ear and no response in the left. Sensory, motor, and reflex examination of the extremities gave normal results. The patient was oriented but had difficulty with arithmetic. Electromyography dem¬ onstrated fibrillation potentials in the right frontalis, zygomaticus, and orbicularis oculi muscles. The right facial nerve could not be stimulated. ElectroencephaloA
Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/13/2015
was mildly abnormal with excessive diffuse and shifting minor theta bursts. Skull x-ray films were normal. Chest roentgenogram showed right apical pleural scar¬ ring. A right internal carotid arteriogram was normal. Cerebrospinal fluid contained one RBC and four WBCs per cubic milli¬
gram
meter; protein, 59 mg/100 ml; glucose, 52 mg/100 ml, with a concurrent blood glucose level of 60 mg/100 ml. There was no growth of bacteria, fungi, or mycobacteria. Colloi¬ dal gold and VDRL tests were negative. An isotopie brain scan was normal. Serum
protein electrophoresis disclosed the fol¬ lowing values: total protein, 7.6 gm/100 ml; albumin, 47.6%; ,-globulin, 23.3%. By
radial immunodiffusion IgA was 395 mg/ 100 ml (normal, 40 to 364); IgM, 230 mg/100 ml (normal, 10 to 270); and IgG, 2,000 mg/ 100 ml (normal, 660 to 1,700). Hemogram and erythrocyte sedimentation rate were normal. Latex rheumatoid arthritic factor was positive at a titer of 1:160, cold agglutinin titer was 1:80, and antinuclear anti¬ body was negative. A culture from the right middle ear showed coagulase-negative staphylococci. Candida and Trichophyton skin tests showed positive delayed hypersensitivity. Prednisone therapy, 60 mg/day, was initiated. Optic nerve swell¬ ing diminished in 17 days and the patient was discharged on the 49th hospital day. Prednisone administration was discontin¬ ued after two months. Three years later, he was readmitted with complaints of difficulty walking, talk¬ ing, and swallowing and an 11.4-kg weight loss over the preceding four months. The patient was alert; his speech was unintelli¬ gible. He responded to simple commands
Fig 1.—Transverse section hyde-fixed cerebellum has
of formalde¬ infiltration of white matter and dentate nuclei by lymphomatoid granulomatosis. Central pons is also involved (x 1).
and identified
pointing
some
objects correctly by
at them.
Visual fields were normal to confrontation by finger motion. The right pupil was larger than the left, and ptosis was present on the right. There was unsustained slow nystagmus of the abducting eye when right horizontal gaze was attempted; otherwise, lateral eye movements were absent and there was marked limitation of upward and down¬ ward gaze. There was bilateral hearing loss and complete right-sided, peripheral facial weakness. Functions of other cranial nerves were normal. Generalized muscle weakness was pres¬ ent in all extremities, somewhat greater on the left. Tone was generally increased. There were fasciculations in the right thigh. Muscle stretch reflexes were hyper¬ active and symmetrical; the plantar re¬ flexes were bilaterally extensor. Electro¬ myography showed 3+ fibrillations, posi¬ tive waves, and fasciculations in all four extremities. Motor nerve conduction veloci¬ ties were normal. An electroencephalo¬ gram was again mildly abnormal. A right internal carotid and left vertebral arteriography and an isotopie brain scan were normal. Pneumoencephalogram showed mild dilation of all ventricles, and very little air was seen over the convexity. The first cerebrospinal fluid specimen was obtained before instillation of air. No RBCs and three mononuclear WBCs were detected. Other values were as follows: glucose, 57 mg/100 ml; protein, 47 mg/100 ml; IgG, 6.4 mg/100 ml; albumin, 16.5 mg/ 100 ml; IgG-albumin ratio; 1:2.6. No growth occurred in cultures. A second cerebro¬ spinal fluid evaluation five days later disclosed seven RBCs and three WBCs; protein, 53 mg/100 ml; and glucose, 51 mg/ 100 ml. IgG level was 8.4 mg/100 ml, and albumin concentration was 14 mg/100 ml with a ratio of 1:1.7. VDRL test was nega¬ tive. Anaerobic culture yielded Propioni-
Fig 2.—Destructive lesion of central pons with loss of myelinated tracts Atypical lymphoreticular cells cuff vessels (Luxol fast blue, 200). bacterium
acnes.
Chest roentgenogram
unchanged from that obtained during the first hospitalization. Admission labora¬ was
tory studies disclosed
a low serum potas¬ sium level, which improved during hospi¬ talization. Serum protein electrophoresis showed the following values: total protein, 7.7 gm/100 ml, with albumin, 42.8%,
