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ALERTS, NOTICES, AND CASE REPORTS
ALERTS,
Intractable Hiccups as a Presentation of Central Nervous System Sarcoidosis LCDR JOHN P. CONNOLLY, MC, USN LT TIMOTHY J. CRAIG, MC, USN LCDR RAMON M. SANCHEZ, MC, USN LCDR W. SCOrT SAGEMAN, MC, USN LCDR ROBIN E. OSBORN, MC, USN San Diego, California
HiccUPS ARE MOST OFTEN TRANSIENT and resolve without therapy. The differential diagnosis of persistent hiccups, however, is very long' (Table 1), and neurosarcoidosis has been suggested only once previously as a cause.2 We report the case of a patient with biopsy-proven sarcoidosis in whom persistent hiccups developed as the first sign of recurrence in the central nervous system. Report of a Case
The patient, a 25-year-old man, was diagnosed in May 1987 with uveitis, peripheral facial nerve palsy, and bihilar adenopathy on chest x-ray film. Sarcoidosis was diagnosed by transbronchial lung biopsy. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain were normal. The patient initially did well with a tapering course of prednisone over six months ending December 1987. In August 1988, he again sought medical care for weight loss, malaise, and persistent hiccups, which were TABLE 1.-Commonly Reported Causes of Persistent Hiccups Metabolic Electrolyte imbalance Renal failure Alcohol ingestion Diabetes mellitus Central nervous system Tumors Trauma or surgical procedure Infections Vascular lesions
Multiple sclerosis
Peripheral nervous system (branches of
vagus nerve) Diaphragmatic irritation Tympanic membrane irritation Thoracic, ENT, or abdominal tumors Thoracic, ENT, or abdominal infections Drugs Psychogenic Idiopathic ENT= ears, nose, and throat
(Connolly JP, Craig TJ, Sanchez RM, Sageman WS, Osborn RE: Intractable hiccups as a presentation of central nervous system sarcoidosis. West J Med 1991 Jul; 155:78-79) From the Departments of Internal Medicine (Pulmonary Division) (Drs Connolly, Craig, and Sageman), Neurology (Dr Sanchez), Radiology and Clinical Investigation (Dr Osborn), Naval Hospital, San Diego, California. Dr Connolly is currently with the Naval Hospital, Pensacola, Florida. The work reported herein was performed under the Navy Clinical Investigation Program, case report No. 84-16-1968-131. The views expressed in this article are those of the authors and do not necessarily reflect the views of the Department of the Navy, Department of Defense, or the United States government. Reprint requests to LCDR J. P. Connolly. MC, USN. c/o Clinical Investigation Department. Naval Hospital, San Diego, CA 92134-5000.
NOTICES,
AND
CASE
REPORTS
ABBREVIATIONS USED IN TEXT CT = computed tomography MRI = magnetic resonance imaging
unresponsive to multiple trials of metoclopramide hydrochloride, chlorpromazine hydrochloride, phenytoin sodium, and quinidine sulfate. A month later he noted bilateral lower extremity weakness and worsening of his hiccups. Physical examination showed a grossly ataxic gait and a notable (3 to 4/5) bilateral upper and lower extremity weakness. Urinary retention subsequently developed. A cranial CT scan was again normal. An MRI of the brain and spinal cord showed nodular thickening of the leptomeninges consistent with sarcoidosis (Figures 1 to 3). Polyneuropathy was evident on nerve conduction study results. The cerebrospinal fluid was remarkable for a protein level of 3,210 grams per liter, glucose level of 1.5 mmol per liter, and 248 mononuclear cells per A1. The patient was placed on a regimen of prednisone at 1 mg per kg per day for neurosarcoidosis. Within 48 hours his hiccups resolved. Over the next few weeks his motor strength increased and walking improved. Following three months of therapy, a repeat MRI also showed that the patient had improved. Discussion
Approximately 5% of patients with sarcoidosis have neurologic involvement.3`5 In half of these patients, the neurologic manifestation is the initial presentation of the overall disease.356 Many of the neurologic manifestations of sarcoidosis, especially cranial nerve palsies and endocrine abnormalities, can be traced to basilar sarcoid meningitis.7 Neurosarcoidosis has often been described as having a relapsing or remitting course. The unusual aspect of our case is the manifestation of recurrent disease. The largest series of patients with neurosarcoidosis3"4 reports no cases of hiccups as a presenting problem. Souadjian and Cain reviewed 220 cases of intractable hiccups and outlined all associated diseases.8 Only one patient in this large series was noted to have sarcoidosis. Lewis did not list sarcoidosis in more than 100 causes of persistent hiccups.' Kondo and co-workers reported a patient with sarcoidosis with persistent hiccups responsive to steroid treatment.2 They attributed the hiccups to central nervous system involvement but were unable to confirm this by CT scan or MRI. In our patient, the MRI showed meningeal involvement characteristic for sarcoidosis in the region of multiple cranial nerves as well as surrounding the presumed "hiccup center" in the midbrain or high cervical spinal cord. This region previously has been implicated on electromyography and other studies as being critical in the neural pathways involved in hiccups.910 A cranial CT scan was not as sensitive for this process and did not establish the diagnosis. The response of neurosarcoidosis to steroid therapy has been reported to be variable,'5 but at least half of patients have a good clinical response to steroid therapy that may be long-lasting.' The rapid response of our patient's hiccups and his polyneuropathy to steroid therapy supports the contention that both symptoms were neurologic manifestations of sarcoidosis. Characteristic findings on MRI with improvement on repeated imaging during therapy helped to confirm this clinical impression.
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Figure 1.-A postgadolinium-enhanced coronal brain magnetic resonance image shows enlarged, enhancing fifth cranial nerves (arrows) (SE 500/20).
~~~~~~~~~~~~~~~~~~~~~~~~
V-t ~~~ ' t~~~~~~~ I.
i
~~1W7fJ~..S, ..
Figure 2.-The basilar meningeal involvement is seen as irregular, nodular enhancement (arrows) on this coronal brain image (SE 500/ 20).
gadolin~ium contrast
REFERENCES Lewis JH: Hiccups: Causes and cures. J Clin Gastroenterol 1985: 7:539-552 2. Kondo T. Tanigaki T. Suzuki H. Tamaya S. Ohta Y. Yamabayashi H: Longstanding hiccup in a patient with sarcoidosis. Jpn J Med 1989; 28:212-215 3. Stern BJ. Krumholz A. Johns C. Scott P. Nissin J: Sarcoidosis and its neurological manifestations. Arch Neurol 1985: 42:909-917 4. Delaney P: Neurologic manifestations in sarcoidosis: Review of the literature with a report of 23 cases. Ann Intern Med 1977: 87:336-345 5. Oksanen V: Neurosarcoidosis: Clinical presentations and course in 50 patients. Acta Neurol Scand 1986a 73:283-290 _.
Figure 3.-A midline sagittal magnetic resonance image of the cervical spinal cord using gadolinium also shows nodular meningeal enhancement (arrows) (SE 800/20).
6. Pentland B. Mitchell JD. Cull RE. Ford MJ: Central nervous system sarcoidosis. Q J Med 1985: 56:457-465 7. Cahill DW. Salcman M: Neurosarcoidosis: A review of the rarer manifestations. Surg Neurol 1981: 15:204-21 1 8. Souadjian JV. Cain JC: Intractable hiccup: Etiologic f:actors in 220 cases. Postgrad Med 1968: 43:72-77 9. Nathan MD. Leshner RT. Keller AP Jr: Intractable hiccups (singultus). Laryngoscope 1980: 90:1612-1618 10. Newsomil-Davis J: An experiniental study ot hiccups. Brain 1970: 93:851-872
ALERTS, NOTICES, AND CASE REPORTS
ALERTS,
Intractable Hiccups as a Presentation of Central Nervous System Sarcoidosis LCDR JOHN P. CONNOLLY, MC, USN LT TIMOTHY J. CRAIG, MC, USN LCDR RAMON M. SANCHEZ, MC, USN LCDR W. SCOrT SAGEMAN, MC, USN LCDR ROBIN E. OSBORN, MC, USN San Diego, California
HiccUPS ARE MOST OFTEN TRANSIENT and resolve without therapy. The differential diagnosis of persistent hiccups, however, is very long' (Table 1), and neurosarcoidosis has been suggested only once previously as a cause.2 We report the case of a patient with biopsy-proven sarcoidosis in whom persistent hiccups developed as the first sign of recurrence in the central nervous system. Report of a Case
The patient, a 25-year-old man, was diagnosed in May 1987 with uveitis, peripheral facial nerve palsy, and bihilar adenopathy on chest x-ray film. Sarcoidosis was diagnosed by transbronchial lung biopsy. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain were normal. The patient initially did well with a tapering course of prednisone over six months ending December 1987. In August 1988, he again sought medical care for weight loss, malaise, and persistent hiccups, which were TABLE 1.-Commonly Reported Causes of Persistent Hiccups Metabolic Electrolyte imbalance Renal failure Alcohol ingestion Diabetes mellitus Central nervous system Tumors Trauma or surgical procedure Infections Vascular lesions
Multiple sclerosis
Peripheral nervous system (branches of
vagus nerve) Diaphragmatic irritation Tympanic membrane irritation Thoracic, ENT, or abdominal tumors Thoracic, ENT, or abdominal infections Drugs Psychogenic Idiopathic ENT= ears, nose, and throat
(Connolly JP, Craig TJ, Sanchez RM, Sageman WS, Osborn RE: Intractable hiccups as a presentation of central nervous system sarcoidosis. West J Med 1991 Jul; 155:78-79) From the Departments of Internal Medicine (Pulmonary Division) (Drs Connolly, Craig, and Sageman), Neurology (Dr Sanchez), Radiology and Clinical Investigation (Dr Osborn), Naval Hospital, San Diego, California. Dr Connolly is currently with the Naval Hospital, Pensacola, Florida. The work reported herein was performed under the Navy Clinical Investigation Program, case report No. 84-16-1968-131. The views expressed in this article are those of the authors and do not necessarily reflect the views of the Department of the Navy, Department of Defense, or the United States government. Reprint requests to LCDR J. P. Connolly. MC, USN. c/o Clinical Investigation Department. Naval Hospital, San Diego, CA 92134-5000.
NOTICES,
AND
CASE
REPORTS
ABBREVIATIONS USED IN TEXT CT = computed tomography MRI = magnetic resonance imaging
unresponsive to multiple trials of metoclopramide hydrochloride, chlorpromazine hydrochloride, phenytoin sodium, and quinidine sulfate. A month later he noted bilateral lower extremity weakness and worsening of his hiccups. Physical examination showed a grossly ataxic gait and a notable (3 to 4/5) bilateral upper and lower extremity weakness. Urinary retention subsequently developed. A cranial CT scan was again normal. An MRI of the brain and spinal cord showed nodular thickening of the leptomeninges consistent with sarcoidosis (Figures 1 to 3). Polyneuropathy was evident on nerve conduction study results. The cerebrospinal fluid was remarkable for a protein level of 3,210 grams per liter, glucose level of 1.5 mmol per liter, and 248 mononuclear cells per A1. The patient was placed on a regimen of prednisone at 1 mg per kg per day for neurosarcoidosis. Within 48 hours his hiccups resolved. Over the next few weeks his motor strength increased and walking improved. Following three months of therapy, a repeat MRI also showed that the patient had improved. Discussion
Approximately 5% of patients with sarcoidosis have neurologic involvement.3`5 In half of these patients, the neurologic manifestation is the initial presentation of the overall disease.356 Many of the neurologic manifestations of sarcoidosis, especially cranial nerve palsies and endocrine abnormalities, can be traced to basilar sarcoid meningitis.7 Neurosarcoidosis has often been described as having a relapsing or remitting course. The unusual aspect of our case is the manifestation of recurrent disease. The largest series of patients with neurosarcoidosis3"4 reports no cases of hiccups as a presenting problem. Souadjian and Cain reviewed 220 cases of intractable hiccups and outlined all associated diseases.8 Only one patient in this large series was noted to have sarcoidosis. Lewis did not list sarcoidosis in more than 100 causes of persistent hiccups.' Kondo and co-workers reported a patient with sarcoidosis with persistent hiccups responsive to steroid treatment.2 They attributed the hiccups to central nervous system involvement but were unable to confirm this by CT scan or MRI. In our patient, the MRI showed meningeal involvement characteristic for sarcoidosis in the region of multiple cranial nerves as well as surrounding the presumed "hiccup center" in the midbrain or high cervical spinal cord. This region previously has been implicated on electromyography and other studies as being critical in the neural pathways involved in hiccups.910 A cranial CT scan was not as sensitive for this process and did not establish the diagnosis. The response of neurosarcoidosis to steroid therapy has been reported to be variable,'5 but at least half of patients have a good clinical response to steroid therapy that may be long-lasting.' The rapid response of our patient's hiccups and his polyneuropathy to steroid therapy supports the contention that both symptoms were neurologic manifestations of sarcoidosis. Characteristic findings on MRI with improvement on repeated imaging during therapy helped to confirm this clinical impression.
THE WESTERN JOURNAL OF MEDICINE
-
JULY 1991
0
155
o
1
79
79
Figure 1.-A postgadolinium-enhanced coronal brain magnetic resonance image shows enlarged, enhancing fifth cranial nerves (arrows) (SE 500/20).
~~~~~~~~~~~~~~~~~~~~~~~~
V-t ~~~ ' t~~~~~~~ I.
i
~~1W7fJ~..S, ..
Figure 2.-The basilar meningeal involvement is seen as irregular, nodular enhancement (arrows) on this coronal brain image (SE 500/ 20).
gadolin~ium contrast
REFERENCES Lewis JH: Hiccups: Causes and cures. J Clin Gastroenterol 1985: 7:539-552 2. Kondo T. Tanigaki T. Suzuki H. Tamaya S. Ohta Y. Yamabayashi H: Longstanding hiccup in a patient with sarcoidosis. Jpn J Med 1989; 28:212-215 3. Stern BJ. Krumholz A. Johns C. Scott P. Nissin J: Sarcoidosis and its neurological manifestations. Arch Neurol 1985: 42:909-917 4. Delaney P: Neurologic manifestations in sarcoidosis: Review of the literature with a report of 23 cases. Ann Intern Med 1977: 87:336-345 5. Oksanen V: Neurosarcoidosis: Clinical presentations and course in 50 patients. Acta Neurol Scand 1986a 73:283-290 _.
Figure 3.-A midline sagittal magnetic resonance image of the cervical spinal cord using gadolinium also shows nodular meningeal enhancement (arrows) (SE 800/20).
6. Pentland B. Mitchell JD. Cull RE. Ford MJ: Central nervous system sarcoidosis. Q J Med 1985: 56:457-465 7. Cahill DW. Salcman M: Neurosarcoidosis: A review of the rarer manifestations. Surg Neurol 1981: 15:204-21 1 8. Souadjian JV. Cain JC: Intractable hiccup: Etiologic f:actors in 220 cases. Postgrad Med 1968: 43:72-77 9. Nathan MD. Leshner RT. Keller AP Jr: Intractable hiccups (singultus). Laryngoscope 1980: 90:1612-1618 10. Newsomil-Davis J: An experiniental study ot hiccups. Brain 1970: 93:851-872
