Letter to Editor Uncommon manifestations of neurosarcoidosis

Sir Neurological manifestations in , a multisystem granulomatous disease with enhanced cellular immune proc- ess at the site of disease activity, occur in 5% to 6% patients with sarcoidosis.1,3 A 52-year-old male developed left-sided lower motor neu- ron type of palsy, which responded to steroid therapy. Two months later, the patient developed dysarthria, Figure 1: Transbronchial showing discrete non-caseating difficulty in swallowing and nasal regurgitation of fluids. epitheloid cell (arrows) [hematoxylin and eosin x 144] He gave history of cough, expectoration and wheezing with seasonal exacerbations, responding to bronchodilators and steroids for the past 30 years. He was treated with long- term steroids for allergic bronchopulmonary aspergillosis (ABPA). Examination revealed residual left VII nerve paresis with evidence of right-sided IX and X nerve palsy and partial involvement of right XI nerve. There was pansensory loss on the trunk involving the D5 to D8 region on the left side. The ankle reflexes were absent bilaterally with mild im- pairment of touch, joint position and vibration sensation in the upper and lower limbs in a glove and stocking distri- Figure 2: Sural nerve biopsy showing non-caseating granulomas with bution. Nerve conduction studies revealed evidence of sym- Langhan’s giant cells and lymphocytic infiltration (arrows) metrical axonal sensorimotor neuropathy, predominantly [hematoxylin and eosin x 288] involving the lower limbs. Transbronchial lung biopsy and nerve biopsy of the right sural nerve revealed non-caseat- of neurosarcoidosis patients.9 Though commonly unilateral, ing granulomas with giant cell formation consistent with bilateral facial palsy can occur simultaneously or sequentially the diagnosis of sarcoidosis (Figures 1 and 2). The patient in approximately one-third of the patients.10 Other cranial was initially treated with oral in the dose of nerves, especially the IX and X are less commonly affected.9 1mg/kg/day for 4 weeks followed by gradual tapering to a The pattern of non-cranial includes dose of 10 mg every alternate day. Subsequently, chloro- patchy neuropathy or mononeuritis, a component of which quine at a dose of 150 mg b.i.d/day was added with regular may be an `intercostal neuritis’ with numb patches on the monitoring of visual impairment. The patient showed re- trunk (as seen in the present case), acute Guillaine-Barre markable clinical improvement in bulbar symptoms and syndrome (GBS), and chronic sensorimotor, motor or pure truncal pain within 2 weeks of starting the therapy, with sensory neuropathies.3,11,12 Of these, chronic symmetric ax- gradual improvement thereafter. onal sensorimotor polyneuropathy is most commonly ob- Neurosarcoidosis can manifest in myriad ways including served.12 A combination of multiple cranial and non-cranial cranial neuropathy, aseptic , mass lesions, en- neuropathies was also observed in our patient. Sensorimo- cephalopathy, vasculopathy, , psychiatric manifes- tor neuropathy has been attributed to epineural and tations, , hypothalamic pituitary disorders, my- perineural granulomas with an associated granulomatous elopathy, peripheral neuropathy and myopathy.3,4-6 The mode vasculitis, producing an axonal degeneration with associated of onset of neurosarcoidosis is variable, but it is usually su- demyelination.12,13 Although non-caseating granulomas are bacute to chronic. Acute onset neurological disease usually rarely observed in nerve biopsy samples,13 the sural nerve presents with isolated cranial neuropathies and aseptic men- biopsy in our patient revealed these characteristic changes ingitis, while patients with a chronic onset usually present (Figure 2). with parenchymal involvement, hydrocephalus or peripheral Unlike pulmonary sarcoidosis where a period of observation nervous system manifestations.7 Cranial neuropathy is the is recommended for mild and asymptomatic cases, most common manifestation of neurosarcoidosis occurring neurosarcoidosis should always be treated.14 Treatment deci- in up to 75% of the patients.8 The facial nerve is the most sions are governed by disease location, clinical severity, time commonly affected cranial nerve and is involved in up to 50% course and morbidity of treatment. Corticosteroids are the

280 India June 2004 Vol 52 Issue 2 280 CMYK Letter to Editor cornerstone of the therapy for neurosarcoidosis. Steroid 15. Agbogu BN, Stern BJ, Sewell C, et al Therapeutic considerations in patients with refractory neurosarcoidosis. Arch Neurol 1995;52:875-9. therapy is usually started at a high dose and after achieving a 16. Sharma OP. Effectiveness of chloroquine and in treating clinical response, the dose is gradually tapered.14 Alternative selected patients with sarcoidosis with Neurological involvement. Arch Neurol 1998;55:1248-54. therapeutic agents are indicated in patients with steroid side- effects or lack of response to treatment or in cases where ster- Accepted on 14.12.2002. oids are contraindicated. These include cyclosporine, azathio- prine, hydroxychloroquine, chloroquine and .15 Chloroquine and hydroxychloroquine have been found to be effective in controlling neurosarcoidosis in pa- tients who fail to respond to corticosteroids or develop serious Trigger autoimmunity - side-effects, with no evidence of ocular toxicity during the treat- ment.16 Clinical manifestations are the best predictors of the Development of multiple course and prognosis in patients with neurosarcoidosis.16 Cra- plexopathy in a patient with nial neuropathies and carry the best prog- nosis with recovery in up to 90% of cases.9,10 Approximately chronic idiopathic 32% of the patients with neurosarcoidosis, especially those with cranial neuropathies, relapse after the initial neurologi- thrombocytopenic purpura cal episode.11 Patients with parenchymal disease generally have a prolonged disease course with significant morbidity. Among Sir, the peripheral nervous system manifestations, polyradiculitis A case of chronic idiopathic thrombocytopenic purpura and acute myopathy tend to respond well to steroids compared (ITP) who developed plexopathy, mellitus and tran- to the slowly progressive peripheral neuropathy and myopa- sient disseminated intravascular coagulation (DIC) after thy.10 splenectomy during hospitalization for the treatment of ITP is presented. M. Modi, R. Bhatia*, R. Jain, V. Lal, B. D. A 42-year-old man diagnosed to be having chronic ITP was Radotra,** A. Aggarwal*** admitted for elective splenectomy, for a steroid-responsive but dependent status. His diagnosis was reconfirmed during the Departments of Neurology, *Asst. Professor, Dept. of Neurology, Neurosciences Centre, AIIMS, New Delhi.,**Pathology and preoperative period. He underwent splenectomy. On the third ***Pulmonary Medicine, Postgraduate Institute of Medical Educa- postoperative day, his blood sugar was 348 mg/dl with the pres- tion and Research, Chandigarh - 160012, India. ence of urinary ketones, and arterial blood gas (ABG) revealed E-mail: [email protected] metabolic acidosis. He was treated with plain porcine insulin, References intravenous fluid and electrolytes. His ketoacidosis was con- trolled with a total of 40 U of plain insulin. During the postop-

1. John CJ, (Ed). Tenth International Conference on sarcoidosis and other erative period his platelet counts remained at 20-24000/cumm, granulomation disorders. Ann NY Acad Sc 1986;465:1. while peripheral smear revealed fragmented RBCs and throm- 2. Chapelan C, Uzzar B, Piette JCh, et al. Sarcoidosis in Internal Medicine: A cooperative study of 554 cases. Ann Med Intern 1984;135:125-31. bocytopenia. Paracoagulation test for fibrinogen degradation 3. Stern BJ, Krumholz A, Johns C. Sarcoidosis and its neurological manifesta- product (FDP) was positive with prolonged prothrombin time tions. Arch Neurol 1985;42:909-17. 4. Wiederholt WC, Siekert RG. Neurological manifestations of sarcoidosis. Neu- (test 21 min; control 13 min). DIC was diagnosed for which he rology 1965;19:1147-54. received fresh frozen plasma (FFP) and platelet packs. Multi- 5. Pentland B, Mitchell JD, Cull RE, Ford MJ. Sarcoido- sis. Quart J Med 1985;56:457-65. ple blood cultures, urine cultures, cultures from the site of sur- 6. Younger DS, Hayo AP, Brust JC, Rawland LP. Granulomatous angiitis of the gery were negative. On the fifth postoperative day he complained brain. An inflammatory reaction of diverse etiology. Arch Neurol 1988;45:514- 8. of weakness and numbness of the right upper limb. Clinical 7. Luke RA, Stern BJ, Krumholz A, et al. Neurosarcoidosis: The long term clini- examination revealed lower motor neuron weakness and wast- cal course. Neurology 1987;37:461-3. 8. Delaney P. Neurologic manifestations in Sarcoidosis: Review of literature, with ing of the following muscles: in the upper limb on the right side report of 23 cases. Ann Intern Med 1977;87:336-45. serratus anterior, pectoralis major, supraspinatus, infraspina- 9. Chapelon C, Ziza JM, Piette JC, et al. Neurosarcoidosis: Sign, course and treat- ment in 35 confirmed cases. Medicine (Baltimore) 1990;69:261-76. tus, latissimus dorsi and teres major while on the left side, 10. Oksanen V. Neurosarcoidosis: Clinical presentation and course in 50 patients. muscles of the thenar and hypothenar group, dorsal and pal- Acta Neurol Scand 1986;73:283-90. 11. Scott TF. Neurosarcoidosis. Progress and clinical aspects. Neurology 1993;43:8- mar interossei, and the lumbricals were involved. He had a loss 12. of all sensory modality over the right forearm, hand, lower 1/ 12. Zuniga G, Ropper AH, Frank J. Sarcoid peripheral neuropathy. Neurology 3rd of the right arm and the ulnar border of the left hand and 1991;41:1558-61. 13. Nemni R, Galassi G, Cohen M, et al. Symmetric sarcoid polyneuropathy: Analy- forearm. Deep tender reflexes were lost in the right upper limb. sis of sural nerve biopsy. Neurology 1981;31:1212-23. Plain radiography, CT thorax and magnetic imaging resonance 14. Hunninghake GW, Gilbert S, Pueringer R, et al. Outcome of the treatment of Sarcoidosis. Ann J Respir care Med 1994;149:893-8. (MRI) of the spine were normal. CSF study was normal.

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