Hydrocephalus as a presenting manifestation of neurosarcoidosis. (Case Report).

Abstract: We present a case of hydrocephalus as the primary manifestation of neurosarcoidosis. Neurologic involvement is a significant cause of morbidity and mortality in patients with sarcoidosis. Detection and management of neurosarcoidosis remains problematic. Although the typical presentation of facial nerve palsy in a documented case of sarcoidosis is not a diagnostic dilemma, more atypical presentations such as hydrocephalus with increased intracranial pressure in a previously healthy patient can be a challenge.

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Sarcoidosis is a chronic, multisystemic disorder of unknown cause characterized by an accumulation of T lymphocytes and mononuclear phagocytes, noncaseating epithelioid granulomas, and derangement of normal tissue architecture in affected organs. This disease results from an exaggerated cellular immune response (acquired, inherited, or both) to a limited class of persistent antigens or self-antigens and to an exaggerated T-helper lymphocyte immune process. (1) Blacks and northern Europeans have the highest incidence of sarcoidosis. The organs most commonly involved are the lungs, skin, eyes, and lymph nodes. Sarcoidosis is usually a self-limiting disease; however, in many individuals, it is a chronic waxing and waning process occurring over many years. Neurosarcoidosis is not as common as other organ involvement in sarcoidosis but is a major cause of morbidity and mortality. Moreover, there are only a few cited case reports of hydrocephalus occurring in neurosarcoidosis. (2) We present a case of hydrocephalus in a patient with severe generalized adenopathy and sarcoidosis.

Discussion

All parts of the nervous system may be affected in sarcoidosis. Neurologic findings are observed in approximately 5% of patients. (3) Seventh nerve involvement with unilateral facial palsy, which usually occurs suddenly and transiently, is the most common finding (50% of patients with neurosarcoidosis). Optic neuritis is the second most common cranial nerve neuropathy. (4) Palate dysfunction, hearing abnormalities, vertigo, papilledema, hypothalamic and pituitary abnormalities, chronic aseptic meningitis, mass-lesion effect, psychiatric disturbances, myopathy, and seizure are other common neurologic manifestations. (3,4) Hydrocephalus is a very uncommon reported finding.

Luke et al (3) reported that 88% of patients had systemic sarcoidosis at the onset of neurologic symptoms. All of these patients ultimately developed multisystemic sarcoidosis. Patients with neurosarcoidosis have significantly more cardiac and eye involvement than others. Central nervous system (CNS) relapses rarely affect an area different from the site of the original manifestation except for the cranial nerves, which change from episode to episode.

Luke et al (3) established criteria for the diagnosis of neurosarcoidosis to include the following: "1) systemic sarcoidosis present and the neurologic illness reasonably attributed to sarcoidosis, with other causes excluded; and 2) other systemic manifestations of sarcoidosis not established, but pathologic examination of neural or muscle tissue or clinical course consistent with sarcoidosis, and no other cause identified."

Another method for diagnosis of neurosarcoidosis established by Lower et al (4) classifies the patients into definite or probable cases. Definitive neurosarcoidosis can be diagnosed when "1) noncaseating granulomas are identified in neurologic tissue, 2) specific magnetic resonance imaging (MRI) findings of the nervous system are combined with increased lymphocyte and protein levels in cerebrospinal fluid, and 3) and patients with sarcoidosis develop otherwise unexplained diabetes insipidus or facial palsy. Nonspecific MRI findings or unexplained peripheral neuropathies are not sufficient to diagnose sarcoidosis. However, if the abnormality improves with a trial of corticosteroids, then it would be considered a presumptive diagnosis of neurosarcoidosis. Patients are excluded if they have an alternative cause for the neurologic symptoms (ie, diabetes mellitus in a patient with peripheral neuropathy)." (4)

Neurosarcoidosis may clinically be mistaken for other diseases such as multiple sclerosis, spinal cord abnormalities, and peripheral neuropathy. Granulomatous disease of the CNS without evidence of pathogens may pose a diagnostic challenge. In one review, almost half of these patients fulfilled the diagnostic criteria for neurosarcoidosis. (5)

Positive CNS MRI results can be found in 65% of patients, but no neurodiagnostic tests alone are pathognoinonic for neurosarcoidosis. (6) The most common abnormalities seen on brain MRI are white matter, periventricular and periaqueductal high signals (50%), leptomeningeal enhancement (45%), and brain parenchyma enhancing mass (25%). (6) Three presentations have been described for the mass lesions: isolated intraparenchymatous mass, multiple nodules, and subdural plaques. (7) Hydrocephalus, lacrimal mass, extraaxial mass, enlarged pituitary stalk, and enhancing clumped nerve roots are other findings. If pituitary stalk and hypothalamus involvement is seen on MRI scan, it is more suggestive of neurosarcoidosis than other diseases. (7)

Lower et a1 (4) recommends that the following tests be performed when evaluating cases of neurosarcoidosis: ophthalmologic examination, endoscopic nasal and sinus examination, body gallium scan to highlight areas of inflammation that can be amenable to biopsy, and muscle MRI for signs of progressive myopathy.

Treatment options are based on the clinical presentation of the patient. Corticosteroids have long been the mainstay of treatment and are the drugs of choice in facial palsy. Neurologic manifestations, except facial palsy, are usually chronic, and agents other than corticosteroids appear to have increased efficacy with lower morbidity. In one study, corticosteroids benefited only 29% of such patients whereas methotrexate successfully treated 61% and cyclophosphamide controlled disease in 90% of assessable patients. (4) Using a methotrexate regimen, a delayed response of up to 6 months is common, but hepatotoxicity is a potential complication.

In a patient with symptomatic hydrocephalus, a ventricular drain is usually lifesaving. Using corticosteroids alone, patients may improve rapidly but are likely to decompensate, requiring emergency shunting. (8) If hydrocephalus associated with neurosarcoidosis is treated with corticosteroids and without a shunt, then the corticosteroids need to be continued at very high doses for a prolonged period. Our patient showed rapid clinical improvement, supporting the efficacy of this combined treatment.

There have been reports of shunt failure secondary to the primary illness. Maniker et al (9) reported a case of multiple shunt failures in a patient with hydrocephalus. After removal, the shunt was found to be occluded with noncaseating granulomatous material that had infiltrated the shunt lumen. In such resistant cases, cranial or spinal irradiation may be needed.

Overall, the prognosis for neurosarcoidosis is good. Ninety percent of the neurologic manifestations remit or improve with time. Of the varied manifestations of neurosarcoidosis, cranial neuropathies have the best prognosis whereas cerebral lesions and hydrocephalus have the worst long-term prognosis.

Conclusion

The neurologic manifestations of sarcoidosis are highly variable, ranging from cosmetic to life threatening. Hydrocephalus is a serious condition associated with CNS involvement of sarcoidosis. Shunting or prolonged steroid treatment is essential and lifesaving as illustrated by our case.

Accepted July 25, 2002.

References

(1.) Crystal RG. Sarcoidosis, in Fauci AS, Braunwald E, Isselbacher KJ (eds): Harrison's Principles of Internal Medicine, New York, McGraw-Hill Health Professions Division, 1998, vol 2, ed 14, pp 1922-1928.

(2.) Nakamura A, Ohara S, Maruyama K, Takei Y, Shindo M, Yanagisawa N. Systemic sarcoidosis: a case of focal hydrocephalus and elevated lysozyme and angiotensin-converting enzyme in the cerebrospinal fluid. J Neural 1999;246:320-322.

(3.) Luke R, Stern B, Krumholz A, Johns CJ. Neurosarcoidosis: the long-term clinical course. Neurology 1987;37:461-463.

(4.) Lower E, Broderick J, Brott T, Baughman RP. Diagnosis and management of neurological sarcoidosis. Arch Intern Med 1997; 157:1864-1868.

(5.) Thomas G, Murphy S, Staunton H, O'Neill S, Farrell MA, Brett FM. Pathogen-free granulomatous diseases of the central nervous system. Hum Pathol 1998;29:l10-115.

(6.) Lexa F, Grossman R. MR of sarcoidosis in the head and spine: spectrum of manifestations and radiographic response to steroid therapy. AJNR Am JNeuroradiol 1994;15:973-982.

(7.) Saltzer 5, Mark A, Atlas S. CNS sarcoidosis: evaluation with contrastenhanced MR imaging. AJNR Am J Neuroradiol 1991;12:1227-1233.

(8.) Foley KT, Howell JD, Junck L. Progression of hydrocephalus during corticosteroid therapy for neurosarcoidosis. Postgrad Med J 1989;65: 481-484.

(9.) Maniker AH, Cho ES, Schulder M. Neurosarcoid infiltration of the ventricular catheter causing shunt failure: a case report. Surg Neurol 1997;48:527-529.

RELATED ARTICLE: Case Report

A 20-year-old black man was admitted to Memorial Health University Medical Center complaining of nausea and nonprojectile vomiting for 3 weeks. The patient also complained of low-grade fevers, night sweats, and a mild dry cough, which had progressively worsened during the past 6 months. Fatigue and an 11.5-kg weight loss were also significant in his history.

He reported a past medical history of extensive adenopathy and bilateral parotid involvement in the past (Fig. 1). Fine-needle aspiration biopsy of a left cervical node 6 months before his recent admission showed noncaseating granulomas (Fig. 2). Excisional biopsy of a right cervical node showed noncaseating granulomas with central necrosis 10 days after the fine-needle aspiration biopsy. Both biopsies were negative for acid-fast bacilli, malignancy, and fungal infection. The patient was then lost to follow-up.

Physical examination revealed a fatigued man with bilateral cervical, submandibular, axillary, and inguinal lymphadenopathy. Cardiac examination was normal except for a heart rate of 46 beats/min. Neurologic examination was within normal limits. Funduscopic examination showed no papilledema or other abnormalities. Mental status examination revealed an oriented patient with a severely blunted affect.

Laboratory values at admission were white blood cell of 4,800/[mm.sup.3] with a differential of 37% neutrophuls, 22% lymphocytes, 22% monocytes, and 17% bands, erythrocyte sedimentation rate of 42 mm/h, calcium level of 10.2 mg/dl, and amylase of 222 U/L (normal, 60-180 U/L). Angiotensin-converting enzyme level was 113 U/L (normal, <40 U/L). The patient was anergic to purified protein derivative. Normal antineutrophil cytoplasmic antibody, cytomegalovirus, and toxoplasma titers were found.

Chest x-ray showed bihilar adenopathy with normal lung parenchyma (Fig. 3). Computed tomography (CT) showed extensive mediastinal, hilar, and paratracheal adenopathy as well as bulky adenopathy in the porta hepatis and retroperitoneum.

Seventy-two hours after admission, his mild headache worsened, and his vision became blurred. CT of the head showed communicative hydrocephalus (Fig. 4). Lumbar puncture revealed an opening pressure of 28 cm [H.sub.2]O. The cerebrospinal fluid had normal protein and cell counts with a negative India ink smear and bacterial latex agglutinations. Acid-fast bacilli and fungal culture of the cerebrospinal fluid were also negative.

To treat the hydrocephalus, a left frontal ventriculostomy was performed with subsequent intracranial pressure monitoring. IV methyl prednisolone was then started at a rate of 40 mg every 6 hours. The patient improved significantly over the next day, so the IV prednisolone was changed to oral prednisone at a dose of 40 mg every 12 hours. A follow-up CT of the head showed marked reduction in hydrocephalus. During a follow-up visit 2 months later, the patient showed marked clinical improvement with substantial reduction in adenopathy and a return to the patient's premorbid personality, which was much more animated.

Key Points

* Neurologic findings occur in 5% of patients with sarcoidosis.

* Hydrocephalus is a rare manifestation of neurosarcoidosis.

* Ventriculostomy and systemic steroids should be considered as primary treatment for a patient with hydrocephalus and neurosarcoidosis.

From the Department of Internal Medicine Education, Memorial Health University Medical Center, Mercer University, Savannah Campus, Savannah, GA.

Reprint requests to Mary Jean Williams, MD, Department of Internal Medicine, Memorial Health University Medical Center, 1101 Lexington Avenue, Savannah, GA 31406. Email: [e-mail]

Copyright [c] by The Southern Medical Association

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