Acta Med Scand 205: 441-444, 1979
Sarcoidosis Presenting with Diabetes Insipidus Followed by Acute Cranial Nerve Syndrome A Case Report Peter F. Bruning, Hans G. Koster, Ruben E. M. Hekster and Willem Luyendijk From the Department of Endocrinology and Metabolic Diseases, the Department of Neurosurgery and the Division of Neuroradiology, the University Medical Centre, Leiden. The Netherlands
ABSTRACT. Diabetes insipidus in a previously healthy 16-year-old girl led to surgical exploration of a pituitary stalk intumescence detected by oxygen cisternography with the use of tomography. Biopsy of the pituitary stalk contained chronically inflamed brain tissue. Subsequent liver and bone biopsies showed characteristic granulomata, confirming the diagnosis of sarcoidosis. Subfrontal craniotomy was followed by a rapidly progressive basal meningoencephalitis with multiple cranial nerve involvement. The need to establish a causal diagnosis in diabetes insipidus is stressed. The rarity of the disorder and the presumed role of subfrontal craniotomy with regard to the flare-up of the sarcoidosis of the brain are discussed. Key words: sarcoidosis, diabetes insipidus, cranial nerve syndrome.
Acta Med Scand 205: 441, 1979.
Approximately 5 % of all sarcoidosis patients show involvement of the central nervous system (12, 13, 16, 17, 20). Although the process may be disseminated all over the brain and spinal cord, the hypothalamic area and cranial nerves appear to be predilection sites for the granulomata (20). Rarely, and presumably after prolonged existence, the inflammation may give rise to mass lesions acting as brain tumours. In this paper a case of sarcoidosis is reported presenting with diabetes insipidus caused by a pea-size pituitary stalk tumour in an otherwise healthy female adolescent. Surgical exploration was followed acutely by serious impairment of several cranial nerves. CASE REPORT A previously healthy 16-year-old girl presented with polyuria and polydipsia in April 1976. Six weeks before she
had had an influenza-like syndrome. The diagnosis of diabetes insipidus was made and treatment with Minrin” (I-deamino-8-o-arginine vasopressin) was successful. The patient was first admitted in Aug. 1976. The history offered no clues to previous head injury, tuberculosis or other infectious disease, except the “bout of influenza” in February. Dependence on Minrin and a vague frontal headache were the only complaints. The existence of diabetes insipidus resulting from ADH deficiency could easily be confirmed. Physical examination revealed no abnormalities. Sexual development (Tanner’s stage IV) was normal. Bone age was consistent with 16 years. There was no galactorrhoea. X-rays of the chest and sellar region were perfectly normal. Laboratory investigation revealed normal ESR, normal blood count and morphology, normal serum proteins, urea nitrogen and creatinine, calcium, alkaline phosphatase, bilirubin, ASAT, ALAT and normal excretion of bromsulphthalein. The functions of the anterior pituitary were tested: free thyroxine index was normal, basal morning prolactin was elevated (54 ng/ml), LH-RH injection was followed by a normal FSH increase and a pronounced rise of LH, insulin-provoked hypoglycaemia resulted in an adequate increase in both cortisol and growth hormone. Ophthalmological examination gave no indication of uveitis, visual field impairment or any other abnormality. Findings at neurological examination were normal. In the search for a possible sellar or suprasellar cause of the diabetes insipidus and hyperprolactinaemia, bilateral carotid arteriography was done and showed no abnormalities. Pneumoencephalography-cisternography using tomography strongly suggested a 5x5 mm intumescence of the pituitary stalk (Fig. I). The cerebrospinal fluid had a normal cell count, glucose and protein content. A tuberculin (PPD) skin test as well as serological tests for brucellosis and toxoplasmosis were negative. In Nov. 1976 the patient was readmitted for follow-up. She still had the same complaints of vague supraorbital headaches and still needed Minrin. She menstruated regu-
Requests for reprints to: Dr P. F. Bruning, Antoni van Leeuwenhoek-ziekenhuis, Plesmanlaan 121, Amsterdam, The Netherlands. Acru Med Scund 205
442
P . F . Bruning et d.
a Fig. 1 . Lateral midline ( u ) and antero-posterior ( b ) tomograms during combined oxygen pneumoencephalogra-
phy-cisternography demonstrates a small expanding lesion in the pituitary stalk.
larly and had been attending school normally. Findings at general physical and neurological examinations were as normal as before. Visual field testing, however, raised suspicion of slight bitemporal upper field defects. The eyes were otherwise normal. The air studies were repeated and gave exactly the same picture as in August without signs of progression. Cerebrospinal fluid was again found to be normal. Anterior pituitary function tests gave normal results with the exception of a definitely subnormal TSH response to TRH injection. The free thyroxine index, however, was unchanged. It was concluded that surgical exploration would offer the best chances for adequate diagnosis and, in case of tumour, for early treatment. Subfrontal craniotomy was performed on Dec. 24. The pituitary stalk was thickened corresponding with the pneumoencephalographic picture. In a biopsy, chronically inflamed brain parenchyma was seen with an extensive lymphocytic infiltrate containing also plasma cells and mast cells. No indication of tumour, fungal infection or tuberculosis could be found. Postoperatively the patient was very apathetic and drowsy. The diabetes insipidus did not change and could be adequately controlled. Five days after surgery bilateral peripheral facial palsy was noted. A rapidly progressive perceptive loss of hearing was observed on the left and, less severely, on the right. There was no vestibular disturbance. The subsequent development of polyneuropathy in both legs was shown by serious impairment of tendon reflexes and sensibility. Loss of the masseter reflex with facial sensory impairment indicated trigeminal involvement. Diplopia was caused by left trochlear palsy. Because of the histological description of the surgical biopsy and the postoperative clinical picture, sarcoidosis of the central nervous system was considered the most likely diagnosis. Skin tests for atypical mycobacteria were negative. After biopsies from the liver and iliac crest and after a normal y Y m bone T ~ scan, prednisone therapy (30 mg
daily) was initiated four weeks after operation. Several well developed non-necrotizing granulomata were seen in the liver and bone biopsy specimens, yielding the convincing evidence for the existence of sarcoidosis. Within a few days after the start of prednisone therapy a remarkable improvement of the general condition was noted. The patient regained alertness and activity. Recovery of the facial palsy took several months. Slight trochlear paresis and sensory loss in face and legs still persisted after 10 months. Visual fields became normal except for slight enlargement of the blind spots. Diabetes insipidus remained unchanged. Both conventional audiometry and electrocochleography combined with acoustically evoked brainstem responses showed complete normalization of hearing on the right side, but persistent damage to the innervation of the basal part of the left cochlea. Because of development of symptoms of hypothyroidism and a subnormal free thyroxine index, thyroxine replacement was given. Prolactin remained elevated also after restoration of the euthyroid condition, and small amounts of milk could be expressed from the breast. Since the operation the patient did not menstruate. Bromocriptin" (2.5 mg three times daily) normalized the serum prolactin level and stopped galactorrhoea, but did not restore menstrual cycles. Like the absence of LH and FSH response to LH-RH, the amenorrhoea was ascribed to the corticoid therapy, which is still being given.
DISCUSSION Diabetes insipidus as the only presenting symptom of sarcoidosis is extremely rare. The results of endocrine testing and local exploration of the sellar and suprasellar region by adequate X-ray studies and subsequent surgery in this case stress the im-
Sarcoidosis, diubetes insipidus and cranial nerve syndrome
portance of these efforts for the explanation of diabetes insipidus. Although a minor proportion of cases remain idiopathic even after thorough clinical testing (14), it will mostly be possible to find a tumour or inflammatory process as a cause if local surgery or head injury cannot be indicted. Surgical exploration was thought to be indicated in our patient since the pituitary stalk thickening could represent a tumour (craniopharyngioma, meningioma, glioma, teratoma, a. o.), a granuloma (histiocytosis X, sarcoidosis, tuberculosis, brucellosis, fungal or protozoan infection), a cyst or an extension of a pituitary adenoma (3, 4, 5). Early tumour extirpation could be complete, and non-surgical therapeutic measures would be hazardous without more precise knowlege about the nature of the abnormal structure. It was due to the diabetes insipidus that this small focus of sarcoidosis was detected. Localized sarcoidosis of the brain sometimes presents with larger conglomerations of granulomata acting like brain tumours (12, 15). More often sarcoidosis inflicting the central nervous system manifests itself as chronic meningoencephalitis and this seldom occurs without previous uveitis, parotitis, pulmonary or skin lesions (4, 6, 8, 9). Still more unusual was the strikingly acute postsurgical deterioration of this patient, suffering from rapidly progressive basal meningoencephalitis. Before surgery no neurological symptoms or cerebrospinal fluid abnormalities existed which could have warned, and during subfrontal exploration no other visible abnormalities were encountered than the thickened pituitary stalk. Very few cases of sarcoidosis involving the central nervous system in which craniotomy was followed by worsening are mentioned in the literature (6, 12, 15). The reason for the flare-up is unclear. If it is accepted that sarcoidosis may be an unfavourable immune response (8) to an as yet unknown and possibly non-specific stimulus, it might be argued that some existing equilibrium was disturbed. Surgery possibly meant “stress” or spilling of antigen and implicated the administration of anaesthetics and a high dosage of hydrocortisone (to protect against ACTH deficiency as a possible result from pituitary stalk surgery) which was tapered off in a few days. It is known that lowering of corticoid dosage in systemic lupus erythematosus or rheumatoid disease bears the risk of acute exacerbation or the onset of vascular manifestations ( I 1, 18). A “bout of influenza” like this patient had
443
shortly before the onset of her diabetes insipidus is described more often as preceding deterioration of existing sarcoidosis ( 2 , 6, 10). It is generally assumed that involvement of the central nervous system is a relatively late manifestation (6). In this case, however, nothing except the flu indicated possible previous disease. Only when the patient deteriorated after craniotomy were liver and bone biopsies taken and revealed generalized disease. In a similar future case, liver biopsy might be considered earlier (1). Spontaneous recovery from sarcoidosis is well known. From the literature it can be concluded that corticoid treatment of sarcoidosis of the nervous system may give at least symptomatic improvement, hopefully also preventing permanent damage (6, 7). As far as already existent neuronal lesions are concerned, no complete recovery can be expected. In our patient partial improvement has been observed. The rapid and steady recovery after corticoid administration suggests a favourable therapeutic effect. The central loss of hearing of the left ear seems to be definitive. Also because of the reported relapses after corticoid withdrawal, this therapy will be continued for at least 2 years at the lowest effective dosage.
REFERENCES 1. Beard, W., Foster, D. B., Kepes, J. J. & Guillan, R. A.: Xanthomatosis of the central nervous system. Neurology (Minneap) 20: 305, 1970. 2. Borner, E.: Lofgren-Syndrom (akuter Morbus Boeck) mit Polyneuritis. Dtsch Med Wochenschr 93: 1654,
1968. 3. Clinicopathological Conference, Case 38-1975. N Engl J Med 292: 653, 1975. 4. Colover, J.: Sarcoidosis with involvement of the nervous system. Brain 71:451, 1948. 5. Crompton, M. R.: In: Pituitary tumours (ed. J. S. Jenkins),chapter 2. Butterworths, London 1973. 6. Douglas, A . C. & Maloney, A. F. J.: Sarcoidosis of the central nervous system. J Neurol Neurosurg Psychiatry 36: 1024, 1973. 7. Findley, L. J.: Relapsing meningo-encephalitis, Cerebral sarcoidosis?Proc R SOCMed 68: 22, 1975. 8. Geraint James, D., Neville, E. & Langley, D. A . : Ocular sarcoidosis. Trans Ophthalmol SOCUK 96: 133, 1976. 9. Geraint James, D. & Sharma, 0. P.: Neurological complications of sarcoidosis. Roc R SOCMed 60:
1169, 1967. Gottlieb, M. B.: Bilateral internal ophthalmoplegia in a patient with sarcoidosis. Br J
10. Henkind, P. &
Ophthalmol57: 792, 1973. Actir Med Scand 205
444
P.F . Bruning et ul.
1 1 . Hess, E. V . & Goldman, J. A.: In: Arthritis and allied
12. 13.
14. 15. 16.
conditions, 8th ed. (ed. J. L. Hollander and D. J . McCarthy, Jr), p. 510. Lea & Febiger, Philadelphia 1972. Holbach, K. H. & Gaddoni, G.: Die Sarkoidose des ZNS als neurochirurgisches Krankheitsbild. Acta Neurochir 24: 121, 1971. Kohout, J. & Schober, W.: Zur Sarkoidose des Zentralnervensystems. Nervenarzt 45: 538, 1974. Moses, A. M., Miller, M. & Streeten, D. H. P.: Pathophysiologic and pharmacological alterations in the release and action of ADH. Metabolism 25: 697, 1976. Norwood, C. W. & Kelly, D. L.: Intracerebral sarcoidosis acting as a mass lesion. Surg Neurol 2: 367, 1974. Schubert, J. C. F., Gullner, H. R., Fischer, M. &
Ar.fri M P Sccind ~ 205
17.
18.
19. 20.
Kropp, R.: Boecksches Sarkoid des Nervensystems. Dtsch Med Wochenschr 96: 945, 1971. Siltzbach, L. E. Geraint James, D., Neville, E.. Turiaf, J., Battesti, J. P., Sharmd, 0. M . P., Hosoda, Y., Mikami, R. & Odaka, M.: Course and prognosis of sarcoidosis around the world. Am J Med 57:847, 1974. Slocumb, C. H.: Rheumatic complaints during chronic hypercortisonism and syndromes during withdrawal of cortisone in rheumatic patients. Mayo Clin Proc 28:655, 1953. Suchenwirth, R.: Klinische Syndrome der Meningo-Encephalitis Besnier-Boeck-Schaumann. Dtsch Med Wochenschr 17:741, 1%3. Urich, H.: Neurological manifestations of sarcoidosis. Practitioner 202: 632, 1969.
Sarcoidosis Presenting with Diabetes Insipidus Followed by Acute Cranial Nerve Syndrome A Case Report Peter F. Bruning, Hans G. Koster, Ruben E. M. Hekster and Willem Luyendijk From the Department of Endocrinology and Metabolic Diseases, the Department of Neurosurgery and the Division of Neuroradiology, the University Medical Centre, Leiden. The Netherlands
ABSTRACT. Diabetes insipidus in a previously healthy 16-year-old girl led to surgical exploration of a pituitary stalk intumescence detected by oxygen cisternography with the use of tomography. Biopsy of the pituitary stalk contained chronically inflamed brain tissue. Subsequent liver and bone biopsies showed characteristic granulomata, confirming the diagnosis of sarcoidosis. Subfrontal craniotomy was followed by a rapidly progressive basal meningoencephalitis with multiple cranial nerve involvement. The need to establish a causal diagnosis in diabetes insipidus is stressed. The rarity of the disorder and the presumed role of subfrontal craniotomy with regard to the flare-up of the sarcoidosis of the brain are discussed. Key words: sarcoidosis, diabetes insipidus, cranial nerve syndrome.
Acta Med Scand 205: 441, 1979.
Approximately 5 % of all sarcoidosis patients show involvement of the central nervous system (12, 13, 16, 17, 20). Although the process may be disseminated all over the brain and spinal cord, the hypothalamic area and cranial nerves appear to be predilection sites for the granulomata (20). Rarely, and presumably after prolonged existence, the inflammation may give rise to mass lesions acting as brain tumours. In this paper a case of sarcoidosis is reported presenting with diabetes insipidus caused by a pea-size pituitary stalk tumour in an otherwise healthy female adolescent. Surgical exploration was followed acutely by serious impairment of several cranial nerves. CASE REPORT A previously healthy 16-year-old girl presented with polyuria and polydipsia in April 1976. Six weeks before she
had had an influenza-like syndrome. The diagnosis of diabetes insipidus was made and treatment with Minrin” (I-deamino-8-o-arginine vasopressin) was successful. The patient was first admitted in Aug. 1976. The history offered no clues to previous head injury, tuberculosis or other infectious disease, except the “bout of influenza” in February. Dependence on Minrin and a vague frontal headache were the only complaints. The existence of diabetes insipidus resulting from ADH deficiency could easily be confirmed. Physical examination revealed no abnormalities. Sexual development (Tanner’s stage IV) was normal. Bone age was consistent with 16 years. There was no galactorrhoea. X-rays of the chest and sellar region were perfectly normal. Laboratory investigation revealed normal ESR, normal blood count and morphology, normal serum proteins, urea nitrogen and creatinine, calcium, alkaline phosphatase, bilirubin, ASAT, ALAT and normal excretion of bromsulphthalein. The functions of the anterior pituitary were tested: free thyroxine index was normal, basal morning prolactin was elevated (54 ng/ml), LH-RH injection was followed by a normal FSH increase and a pronounced rise of LH, insulin-provoked hypoglycaemia resulted in an adequate increase in both cortisol and growth hormone. Ophthalmological examination gave no indication of uveitis, visual field impairment or any other abnormality. Findings at neurological examination were normal. In the search for a possible sellar or suprasellar cause of the diabetes insipidus and hyperprolactinaemia, bilateral carotid arteriography was done and showed no abnormalities. Pneumoencephalography-cisternography using tomography strongly suggested a 5x5 mm intumescence of the pituitary stalk (Fig. I). The cerebrospinal fluid had a normal cell count, glucose and protein content. A tuberculin (PPD) skin test as well as serological tests for brucellosis and toxoplasmosis were negative. In Nov. 1976 the patient was readmitted for follow-up. She still had the same complaints of vague supraorbital headaches and still needed Minrin. She menstruated regu-
Requests for reprints to: Dr P. F. Bruning, Antoni van Leeuwenhoek-ziekenhuis, Plesmanlaan 121, Amsterdam, The Netherlands. Acru Med Scund 205
442
P . F . Bruning et d.
a Fig. 1 . Lateral midline ( u ) and antero-posterior ( b ) tomograms during combined oxygen pneumoencephalogra-
phy-cisternography demonstrates a small expanding lesion in the pituitary stalk.
larly and had been attending school normally. Findings at general physical and neurological examinations were as normal as before. Visual field testing, however, raised suspicion of slight bitemporal upper field defects. The eyes were otherwise normal. The air studies were repeated and gave exactly the same picture as in August without signs of progression. Cerebrospinal fluid was again found to be normal. Anterior pituitary function tests gave normal results with the exception of a definitely subnormal TSH response to TRH injection. The free thyroxine index, however, was unchanged. It was concluded that surgical exploration would offer the best chances for adequate diagnosis and, in case of tumour, for early treatment. Subfrontal craniotomy was performed on Dec. 24. The pituitary stalk was thickened corresponding with the pneumoencephalographic picture. In a biopsy, chronically inflamed brain parenchyma was seen with an extensive lymphocytic infiltrate containing also plasma cells and mast cells. No indication of tumour, fungal infection or tuberculosis could be found. Postoperatively the patient was very apathetic and drowsy. The diabetes insipidus did not change and could be adequately controlled. Five days after surgery bilateral peripheral facial palsy was noted. A rapidly progressive perceptive loss of hearing was observed on the left and, less severely, on the right. There was no vestibular disturbance. The subsequent development of polyneuropathy in both legs was shown by serious impairment of tendon reflexes and sensibility. Loss of the masseter reflex with facial sensory impairment indicated trigeminal involvement. Diplopia was caused by left trochlear palsy. Because of the histological description of the surgical biopsy and the postoperative clinical picture, sarcoidosis of the central nervous system was considered the most likely diagnosis. Skin tests for atypical mycobacteria were negative. After biopsies from the liver and iliac crest and after a normal y Y m bone T ~ scan, prednisone therapy (30 mg
daily) was initiated four weeks after operation. Several well developed non-necrotizing granulomata were seen in the liver and bone biopsy specimens, yielding the convincing evidence for the existence of sarcoidosis. Within a few days after the start of prednisone therapy a remarkable improvement of the general condition was noted. The patient regained alertness and activity. Recovery of the facial palsy took several months. Slight trochlear paresis and sensory loss in face and legs still persisted after 10 months. Visual fields became normal except for slight enlargement of the blind spots. Diabetes insipidus remained unchanged. Both conventional audiometry and electrocochleography combined with acoustically evoked brainstem responses showed complete normalization of hearing on the right side, but persistent damage to the innervation of the basal part of the left cochlea. Because of development of symptoms of hypothyroidism and a subnormal free thyroxine index, thyroxine replacement was given. Prolactin remained elevated also after restoration of the euthyroid condition, and small amounts of milk could be expressed from the breast. Since the operation the patient did not menstruate. Bromocriptin" (2.5 mg three times daily) normalized the serum prolactin level and stopped galactorrhoea, but did not restore menstrual cycles. Like the absence of LH and FSH response to LH-RH, the amenorrhoea was ascribed to the corticoid therapy, which is still being given.
DISCUSSION Diabetes insipidus as the only presenting symptom of sarcoidosis is extremely rare. The results of endocrine testing and local exploration of the sellar and suprasellar region by adequate X-ray studies and subsequent surgery in this case stress the im-
Sarcoidosis, diubetes insipidus and cranial nerve syndrome
portance of these efforts for the explanation of diabetes insipidus. Although a minor proportion of cases remain idiopathic even after thorough clinical testing (14), it will mostly be possible to find a tumour or inflammatory process as a cause if local surgery or head injury cannot be indicted. Surgical exploration was thought to be indicated in our patient since the pituitary stalk thickening could represent a tumour (craniopharyngioma, meningioma, glioma, teratoma, a. o.), a granuloma (histiocytosis X, sarcoidosis, tuberculosis, brucellosis, fungal or protozoan infection), a cyst or an extension of a pituitary adenoma (3, 4, 5). Early tumour extirpation could be complete, and non-surgical therapeutic measures would be hazardous without more precise knowlege about the nature of the abnormal structure. It was due to the diabetes insipidus that this small focus of sarcoidosis was detected. Localized sarcoidosis of the brain sometimes presents with larger conglomerations of granulomata acting like brain tumours (12, 15). More often sarcoidosis inflicting the central nervous system manifests itself as chronic meningoencephalitis and this seldom occurs without previous uveitis, parotitis, pulmonary or skin lesions (4, 6, 8, 9). Still more unusual was the strikingly acute postsurgical deterioration of this patient, suffering from rapidly progressive basal meningoencephalitis. Before surgery no neurological symptoms or cerebrospinal fluid abnormalities existed which could have warned, and during subfrontal exploration no other visible abnormalities were encountered than the thickened pituitary stalk. Very few cases of sarcoidosis involving the central nervous system in which craniotomy was followed by worsening are mentioned in the literature (6, 12, 15). The reason for the flare-up is unclear. If it is accepted that sarcoidosis may be an unfavourable immune response (8) to an as yet unknown and possibly non-specific stimulus, it might be argued that some existing equilibrium was disturbed. Surgery possibly meant “stress” or spilling of antigen and implicated the administration of anaesthetics and a high dosage of hydrocortisone (to protect against ACTH deficiency as a possible result from pituitary stalk surgery) which was tapered off in a few days. It is known that lowering of corticoid dosage in systemic lupus erythematosus or rheumatoid disease bears the risk of acute exacerbation or the onset of vascular manifestations ( I 1, 18). A “bout of influenza” like this patient had
443
shortly before the onset of her diabetes insipidus is described more often as preceding deterioration of existing sarcoidosis ( 2 , 6, 10). It is generally assumed that involvement of the central nervous system is a relatively late manifestation (6). In this case, however, nothing except the flu indicated possible previous disease. Only when the patient deteriorated after craniotomy were liver and bone biopsies taken and revealed generalized disease. In a similar future case, liver biopsy might be considered earlier (1). Spontaneous recovery from sarcoidosis is well known. From the literature it can be concluded that corticoid treatment of sarcoidosis of the nervous system may give at least symptomatic improvement, hopefully also preventing permanent damage (6, 7). As far as already existent neuronal lesions are concerned, no complete recovery can be expected. In our patient partial improvement has been observed. The rapid and steady recovery after corticoid administration suggests a favourable therapeutic effect. The central loss of hearing of the left ear seems to be definitive. Also because of the reported relapses after corticoid withdrawal, this therapy will be continued for at least 2 years at the lowest effective dosage.
REFERENCES 1. Beard, W., Foster, D. B., Kepes, J. J. & Guillan, R. A.: Xanthomatosis of the central nervous system. Neurology (Minneap) 20: 305, 1970. 2. Borner, E.: Lofgren-Syndrom (akuter Morbus Boeck) mit Polyneuritis. Dtsch Med Wochenschr 93: 1654,
1968. 3. Clinicopathological Conference, Case 38-1975. N Engl J Med 292: 653, 1975. 4. Colover, J.: Sarcoidosis with involvement of the nervous system. Brain 71:451, 1948. 5. Crompton, M. R.: In: Pituitary tumours (ed. J. S. Jenkins),chapter 2. Butterworths, London 1973. 6. Douglas, A . C. & Maloney, A. F. J.: Sarcoidosis of the central nervous system. J Neurol Neurosurg Psychiatry 36: 1024, 1973. 7. Findley, L. J.: Relapsing meningo-encephalitis, Cerebral sarcoidosis?Proc R SOCMed 68: 22, 1975. 8. Geraint James, D., Neville, E. & Langley, D. A . : Ocular sarcoidosis. Trans Ophthalmol SOCUK 96: 133, 1976. 9. Geraint James, D. & Sharma, 0. P.: Neurological complications of sarcoidosis. Roc R SOCMed 60:
1169, 1967. Gottlieb, M. B.: Bilateral internal ophthalmoplegia in a patient with sarcoidosis. Br J
10. Henkind, P. &
Ophthalmol57: 792, 1973. Actir Med Scand 205
444
P.F . Bruning et ul.
1 1 . Hess, E. V . & Goldman, J. A.: In: Arthritis and allied
12. 13.
14. 15. 16.
conditions, 8th ed. (ed. J. L. Hollander and D. J . McCarthy, Jr), p. 510. Lea & Febiger, Philadelphia 1972. Holbach, K. H. & Gaddoni, G.: Die Sarkoidose des ZNS als neurochirurgisches Krankheitsbild. Acta Neurochir 24: 121, 1971. Kohout, J. & Schober, W.: Zur Sarkoidose des Zentralnervensystems. Nervenarzt 45: 538, 1974. Moses, A. M., Miller, M. & Streeten, D. H. P.: Pathophysiologic and pharmacological alterations in the release and action of ADH. Metabolism 25: 697, 1976. Norwood, C. W. & Kelly, D. L.: Intracerebral sarcoidosis acting as a mass lesion. Surg Neurol 2: 367, 1974. Schubert, J. C. F., Gullner, H. R., Fischer, M. &
Ar.fri M P Sccind ~ 205
17.
18.
19. 20.
Kropp, R.: Boecksches Sarkoid des Nervensystems. Dtsch Med Wochenschr 96: 945, 1971. Siltzbach, L. E. Geraint James, D., Neville, E.. Turiaf, J., Battesti, J. P., Sharmd, 0. M . P., Hosoda, Y., Mikami, R. & Odaka, M.: Course and prognosis of sarcoidosis around the world. Am J Med 57:847, 1974. Slocumb, C. H.: Rheumatic complaints during chronic hypercortisonism and syndromes during withdrawal of cortisone in rheumatic patients. Mayo Clin Proc 28:655, 1953. Suchenwirth, R.: Klinische Syndrome der Meningo-Encephalitis Besnier-Boeck-Schaumann. Dtsch Med Wochenschr 17:741, 1%3. Urich, H.: Neurological manifestations of sarcoidosis. Practitioner 202: 632, 1969.
