Crystalline encephalopathy cerebral immunoprotein deposits and isolated angiitis – docslide.com.br anoxia refers to

BRIEF COMMUNICATIONS AND CASE REPORTS

Crystalline encephalopathy :

Cerebral irnmunotxotein

DeDosits and

A

Isolated angiitis

G. Pezeshkpour, MD,’ thomas D. Stuart, MD,t

And M. N. Estridge, MDS

Brain biopsy specimens from a 38-year-old woman with

Adversive seizures and bifrontal mass lesions evident

On computed tomographic scans showed extracellular

And intracellular deposits of crystallized proteins. These

Were morphologically identical to the immunoglobulin

Crystals seen in reactive or neoplastic plasma cells and by

Peroxidase-antiperoxidase methods were found to con-

Tain polyclonal immunoglobulins. In addition, severe

Angiitis of the intracerebral blood vessels was present.

Pezeshkpour G, stuart TD, estridge MN:

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Crystalline encephalopathy: cerebral

Immunoprotein deposits and isolated angiitis.

Ann neurol 17:96-99, 1985

Intracellular or extracellular crystallization of im-

Munoglobulins (igs) is a rare event C33. Aside from its

Occurrence in reactive or neoplastic plasma cells, it

Has been reported occasionally in the renal tubular

Epithelium of patients with myeloma [l, 8,91. A much

Rarer condition is the deposition of ig crystals beneath

The corneal epithelium in hyperglobulinemic patienrs,

With or without multiple myeloma: crystalline corneal

Deposits [lo, 13, 16, 17). We report the clinical and

Brain biopsy findings in a nonhyperglobulinemic pa-

Tient with cerebral polyclonal crystallized ig deposits

And isolated central nervous system angiitis.Anoxia refers to

Case report

A previously healthy 38-year-old right-handed woman, a

Homemaker, was admitted with a two-week history of adver-

Sive seizures. These had begun as episodes of head turning to

The right, followed by twitchings of the face and difficulty

With speech. There was no loss of consciousness, inconti-

Nence, or tongue biting.

O n admission she was alert, fully oriented, and coopera-

Tive, with normal vital signs. There were no carotid bruits,

And the cranial nerves were intact. Ophthalmological exami-

From the neuromuscular pathology division, armed forces insti-

Tute of pathology, washington, DC 20306, the tdepartment of

Laboratories, the lovelace medical center, albuquerque, NM

87 108, and the $department of neurosurgery, S t bernadine’s hos-

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Pital, san bernadino, CA 92404.

Received jan 31, 1984, and in revised form april 24. Accepted for

Publication april 27, 1984.

Address reprint requests to dr pezeshkpour.

Nation showed flat optic discs, normal visual fields, and full

Eye movements, and slit-lamp examination showed no abnor-

Malities. There was no dysphagia or dysarthria. The patient

Commanded good motor strength, and there were no cere-

Bellar signs. Deep tendon reflexes and sensory function were

Intact. A 12-channel electroencephalogram made under con-

Ditions of hyperventilation and photic stimulation was nor-

Mal. Isotopic brain scans and contrast computed tomographic

Scans showed two areas of enhancement: one large (5 cm)

Deep-seated right frontal mass and a second smaller and

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More superficially located left frontal lesion, interpreted as

Possible cerebral metastases or bilateral arteriovenous an-

Giomas. Bilateral carotid arteriograms failed to demonstrate

Tumor staining, and there were no narrowings or beading of

The intracerebral arteries. A metastatic bone survey was

Negative.

Results of laboratory investigations including complete

Blood count, ESR, urinalysis, chemistry profile, and repeated

Serum and urine protein electrophoreses and immunoelec-

Trophoreses were normal, and VDRL and antinuclear anti-

Body titers were negative. The patient was started on a

Regimen of diazepam and subsequently was switched to

Phenytoin sodium. Twenty-five days after the first seizure, a

Right frontal craniotomy and partial resection of the deep-

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Seated mass was performed. Because of the firmness of the

Lesion and the fear of breaking into the ventricle, complete

Removal was not attempted. Following a frozen-section diag-

Nosis of granulomatous lesion, intraoperative aspirates of

Intraventricular fluid were obtained and submitted for

Routine analyses, as well as for bacteriological and fungal

Cultures and serological studies.

Postoperatively, repeat sinus and chest roentgenograms,

Sputum, blood, and cerebrospinal fluid cultures, and serolog-

Ical tests for syphilis, various mycoses, parasitoses, and some

Common viruses were done and findings were negative. The

Patient had an uneventful recovery and was discharged on a

Regimen of ethambutol, isoniazid, and pyridoxine.Anoxia refers to

Three months later, despite adequate serum phenytoin

Levels, the adversive seizures returned. At repeat right fron-

Tal craniotomy, the lesion was removed. The second opera-

Tion was tolerated well, and except for mild motor dysfunc-

Tion in the left arm and leg, there was little functional

Impairment. Biopsy materials again failed to reveal any or-

Ganisms.

Six months later, based on the diagnosis of isolated angiitis

Of the central nervous system, the patient was started on

Seven courses of 150 mg of cyclophosphamide a day for four

Of seven consecutive-day periods. There has been no recur-

Rence of the attacks, and a computed tomographic scan one

Year after the discontinuation of cyclophosphamide showed

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Complete resolution of both lesions.

Biopsy specimens were studied extensively with light,

Scanning, and transmission electron microscopy. Microscopic

Sections showed fragments of cortex and white matter punc-

Tuated by prominent extracellular and intracellular crystalline

Deposits (fig 1). These were periodic acid-schiff positive but

Did not polarize with the congo red stain for amyloid. In

Addition, a widespread vasculitic process, involving arteries

And veins of all sizes and sparing only capillaries, was present.

The inflammatory exudate was composed of lymphocytes,

Plasma cells, monocytes, macrophages, and multinucleated

96

Fig I. Widespread deposition in the neuropil of crystallized im-

Munoproteins wi th or without giant cells. (H6E; x 120.)

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(AFIP neg. 83-1 0454.)

Fig 2. Immunoglobulin crystals in the vicinity of a small intrace-

Rebral blood vesjel showing marked intramural inflammdtion.

( H 6 E ; X 280.) (AFIP neg. 83-1 04JJ.)

Giant cells (fig 2). Thrombosis and fibrinoid necrosis of the

Vessel walls were conspicuously absent, and giant cells were

Seen only in the vicinity of the crystalline deposits. The

Intervening neuropil was edematous and gliotic, with no

Areas of hemorrhage or infarction. With the peroxidase-

Antiperoxidase test, the edges of these crystals were reactive

For igg, igm, and iga of both kappa and lambda types.

Albumin, fibrinogen, complement, and lysozyme were ab-

Sent, and there was no reaction in the vessel walls. On elec-

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Tron microscopy, the deposits were seen as both intracellular

And extracellular lamellated (plated) structures regularly

Spaced at 10 to 12 nm intervals (fig 3 ) . When intracellular,

These crystals were bound by a single limiting membrane and

Were morphologically identical to the ig crystals reported in

Reactive and neoplastic plasma cells and in the renal tubular

Fig 3. Electron micrograph of extracellular and intracelhlar

Crystalline deposits. Inset shows the lamelkzted, membrane-bound

Nature of the intrucellzllar cqaals. (uranyl acetate and lead ci-

Trate; X 6,000. Inset, x 40,000.1 (AFIP neg. 83-10456.)

Epithelium, and to the corneal crystalline deposits seen in

Patients with myeloma [l, 10, 13, 16, 171.Anoxia refers to

Discussion

The clinical manifestations of isolated angiitis of the

Central nervous system are nonspecific and range from

Altered mental status to seizures to hemiparesis and

Hemiplegia [ 1, 2 , 4 4 1 . The disease is rarely diagnosed

98 annals of neurology vol 17 no 1 january 1985,

Early; indeed, most cases are diagnosed at postmortem

Examination. At present, cerebral angiography with

The demonstration of a beaded appearance along the

Course of the large intracranial arteries is considered

The diagnostic method of choice [5, 61, although a nor-

Mal arteriogram does not exclude the diagnosis [5-71.

Because involvement of the immune system is docu-

Mented in the pathogenesis of most, if not all, cases of

Vasculitides, a classification of isolated angiitis of the

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Central nervous system (and, for that matter, other vas-

Culitides) based upon involvement of large or small

Vessels seems unjustified [lo]. Prime examples of this

Immune mediation are the demonstration of antielastic

Membrane antibodies in giant cell (temporal) arteritis

And the fact that the central nervous system vasculitis

Of systemic lupus erythematosus may involve large and

Or small blood vessels, simultaneously or at different

Stages of the disease 111, 12, 151. In addition,

Granuloma formation with or without giant cells is

Characteristic of involvement of cell-mediated immune

Mechanisms [141.

In this patient repeated negative cultures of the

Biopsied brain tissue, cerebrospinal fluid, urine, feces,

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And sputum, as well as negative skin tests and serolog-

Ical studies, tend to exclude the likelihood of an infec-

Tious cause for the cerebral vasculitis. In addition,

There was no evidence of an association with systemic

Vascdtides (or their predisposing conditions) or hyper-

Globulinemia (benign or malignant).

The main feature in the two separate brain biopsy

Specimens was a widespread active small-vessel giant-

Cell vasculitis, without fibrinoid necrosis of the vessel

Walls or thrombus formation. The most prominent

Finding, however, was the presence of rather extensive

Intracellular and extracellular polyclonal ig deposits

That morphologically were identical to the ig crystals

Seen in reactive and neoplastic plasma cells and in

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Corneal subepithelial deposits, and to those in the renal

Tubular epithelium of patients with benign monoclonal

Gammopathy and multiple myeloma [l, 10, 13, 16,

171. These cells are usually transformed into multinuc-

Leated syncytial cells 191. Similarly, in our case the mul-

Tinucleated giant cells were found in close association

With the crystalline deposits.

The intriguing aspect of h s case, and probably a key

To the patientâs problem, is the issue of whether these

Crystals have resulted from the leakage of ig(s) through

Damaged blood vessels or whether they represent crys-

Tallization of the locally excreted and/or retained ig

Molecules. It is likely that in the first instance the ig

Deposits would be consequent to the vasculitic process,

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Whereas in the latter situation the reverse might be

True. Immune deposits are known causes of inflamma-

Tory response in many cases of vasculitis, glomerulone-

Phritis, and even choroid plexitis. Finally, it is conceiv-

Able that both the central nervous system angiitis and

The ig deposits represented a localized cerebral hy-

Perergic or autoimmune reaction.

This patientâs response to cyclophosphamide ther-

Apy was dramatic, producing a sustained clinical remis-

Sion. Until recently, isolated angiitis of the central ner-

Vous system has been considered an invariably fatal

Disease. Our experience with this patient is similar to

That of cupps and fauci 151, and we are in agreement

With their consideration of cyclophosphamide therapy

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As the preferred treatment for isolated angiitis of the

Central nervous system.

The opinions or assertions contained herein are the expressed views

Of the authors and are not to be construed as official or as reflecting

The views of the department of the army or the department of

Defense.

References

1. Bessis MC: ultrastructure of lymphoid and plasma cells in rela-

Tion toglobulinandantibody formation. LabInvest 10:1040,1961

2. Budzilovich GN, feigin I, siege1 H: granulomatous angiitis of

The nervous system. Arch pathol 76:250, 1963

3. Connell GE, freedman MH, nyburg SC, et al: A human igg

Myeloma protein crystallizing with rhombohedral symmetry.

Can J biol chem 51:1137, 1973

4. Cravioto H, feigin I: noninfectious granulomatosis angiitis with

anoxia refers to

A predilection for the nervous system. Neurology (minneap)

9:599, 1959

5 . Cupps TR, fauci AS: the vasculitides. In smith LM (ed): major

Problems in internal medicine, vol 2 1. Philadelphia, saunders,

6. Cupps TR, moore PM, fauci AS: isolated angiitis of the central

Nervous system. Am J med 74:97, 1983

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With angiographic abnormalities. Am J roentgen01 fbdiat ther

Nucl med 92:769, 1964

8. It0 S, goshima K, niiomi M, et al: electron microscopy of

Crystalline inclusions in the myeloma cells and kidney of K-

Bence jones protein type myeloma. Acta hematol jpn 33:598,

1970

9. Klintworth GK, bredehoeft SJ, reed JW: analysis of corneal

Crystalline deposits in multiple myeloma.Anoxia refers to am J ophthalmol

86:303, 1978

10. Kolodny EH, rebeiz JJ, caviness VS, richardson EP: granulo-

Matous giant-celled angiitis of the central nervous system. Arch

Neurol 19:510, 1968

11. Liang GC, simkin PA, mannik M: immunoglobulins in tempo-

Ral arteritis. Ann intern med 81:19, 1974

12. Miller KH, green WR, stark WJ, et al: irnmunoprotein depos-

Its in the cornea. Ophthalmology 87944, 1980

13. Moore PM, cupps TR: neurological complications of vasculitis.

Ann neurol 14:155, 1983

14. Nurick S, blackwood W, mair WGP: giant cell granulomatous

Angiitis of the central nervous system. Brain 95:133, 1972

15. Pinkerton RMH, robertson DM: corneal and conjunctival

Changes in dysproteinemia. Invest ophthalmol 8:357, 1969

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16. Rodrigues MM, krachmer JH, miller SD, newsome DA: pos-

Terior corneal crystalline deposits in benign monoclonal gam-

Mopathy. Arch ophthalmol97:124, 1979

17. Vincent FM: granulomatous angiitis. N engl J med 296:452,

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1981, pp 123-132

Case report: pezeshkpour et al: crystalline encephalopathy 99