|Ahead of print publication
Neurosarcoidosis camouflaging as partial miller: Fisher syndrome
BN Shiva Prasad1, Subramanian Ramaswamy2, Aumir Moin3, Srinivas Nalloor4
1 Department of Rheumatology and Immunology, Apollo BGS Hospital, Mysore, Karnataka, India
2 Department of Rheumatology and Immunology, JSS Medical college, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
3 Department of Neurology, Apollo BGS Hospital, Mysore, Karnataka, India
4 Department of Nephrology, Apollo BGS Hospital, Mysore, Karnataka, India
|Date of Submission||23-Jul-2022|
|Date of Acceptance||19-Sep-2022|
|Date of Web Publication||25-Oct-2022|
BN Shiva Prasad,
Apollo BGS Hospital, Mysore, Karnataka
Source of Support: None, Conflict of Interest: None
Neurological involvement in sarcoidosis has varied presentations. Peripheral neuropathy is one of them. Symmetrical axonal type sensory-motor polyneuropathy is the most common form; focal and multifocal neuropathy, polyradiculopathy, and vascular neuropathy are among the others. Cases of demyelinating polyneuropathy masquerading as acute inflammatory demyelinating polyradiculopathy/Guillain–Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy have been reported rarely. Neurosarcoidosis (NS) often masquerades as other disorders, and the occurrence of GBS-like clinical phenotype is a diagnostic challenge. We report a case of NS presenting as atypical GBS.
Keywords: Guillain–Barre syndrome, neurosarcoidosis, noncaseating granuloma
| Introduction|| |
Sarcoidosis is a multisystem inflammatory disease often characterized by the demonstration of noncaseating granulomatous inflammation and/or elevations in the serum angiotensin-converting enzyme levels and less often hypercalcemia. Persistent inflammation in organ tissues may lead to permanent dysfunction if not treated early. Pulmonary sarcoidosis is the most commonly diagnosed form, followed by extrapulmonary presentations. Neurosarcoidosis (NS) is seen in 5%–26% of sarcoidosis patients,, and the manifestations are protean ranging from cranial neuropathies, brain parenchymal involvement, neurovascular, peripheral nerve, and muscular involvement. The other neurologic manifestations include leptomeningitis/pachymeningitis, parenchymal disease often caused by mass lesions, involvement of hypothalamo–pituitary axis, and myopathies. Vascular diseases in sarcoidosis of the central nervous system in isolation are rare. It often occurs early in the course of the disease and is difficult to diagnose in the absence of systemic manifestations. Isolated NS can occur in 10%–20% of the cases.
Guillain–Barre syndrome (GBS)-like presentation of sarcoidosis is rare. A confident diagnosis of sarcoidosis in an acute inflammatory demyelinating disease is difficult. Early facial nerve palsy, papilledema, uveitis, etc., may represent clinical clues toward an NS rather than a Miller Fisher variant of GBS. Here, we report a case of sarcoidosis presenting as GBS.
| Case Report|| |
A 64-year-old male, diabetes mellitus type 2 for the last 10 years presented to the neurology outpatient department with gradually progressive lower limb weakness, imbalance while walking, and giddiness for the last 2 weeks with an increase in severity for 1 week. He had no history of facial weakness, seizures, headache, loss of consciousness, tinnitus, fever, or trauma. There was no recent alcohol, new drug intake, animal (dog) bite, or any infection/diarrhea/vaccination. General and other systemic examinations were normal. No peripheral lymph nodes were palpable. Neurological examination revealed iliopsoas power was 4/5, with absent deep tendon reflexes, and the sensory system being normal. He had ataxia with horizontal nystagmus with left beating and no cranial nerve involvement. On evaluation, hemoglobin (Hb) −11.7 g%, thin layer chromatography (TLC) – 4590/mm3, plat – 2.63 L/mm3, S. creatinine – 1.3 mg/dL (1.4), erythrocyte sedimentation rate (ESR) – 16 mm/1st h, and C-reactive protein (CRP) was negative. Liver and thyroid function tests were normal. HIV, HBSAG, and HCV (ELISA) serology were negative. RF, ANA (IF), ANA profile, ANCA (IF), anti-PR3, and anti-MPO antibodies were also negative. Urine for Bence Jones protein and porphobilinogen were negative. Chest radiographs, ultrasound abdomen, echocardiogram, and ECG were also normal. Magnetic resonance imaging (MRI) of the brain, brain stem, and spine was normal. CSF analysis revealed 13 cells, all lymphocytes, protein 76 mg/dl (15–42), and glucose 61 mg/dl (40–70). CSF analysis for meningoencephalitis panel (polymerase chain reaction [PCR]-based test for herpes simple × 1 and 2, cytomegalovirus, varicella zoster, Mycobacterium tuberculosis, Neisseria meningitidis, and Streptococcus pneumonia) was negative. A nerve conduction study revealed bilateral sensorimotor demyelinating and axonal peripheral neuropathy. Anti-ganglioside ab was negative (both immunoglobulin G [IgG] and immunoglobulin M). He was treated as a variant of GBS, a partial Miller Fisher variant with intravenous immunoglobulins as per protocol. He recovered completely and was discharged. One month later, he came back with a recurrence of the same symptoms: weakness, low back pain, difficulty in walking, giddiness, and ataxia. Clinical finding was like the previous presentation, and in addition, he had right facial lower motor neuron (LMN) palsy. Other systemic, general, and skin were normal. Re-evaluation, Hb − 10.6 g dL, TLC – 5490/mm3, platelet – 2.31 L/mm3, S. creatinine – 1.9 mg/dL, K+−3.3 mmol/L, and Na+−138 mmol/L. Re-evaluation revealed normal liver function test, urine routine, and USG abdomen. Repeat nerve conduction study was same as before. His ESR was 54 mm/1st h, and CRP was 22.2 mg/dl (0–6 mg/dl). Nephrology evaluation for renal impairment revealed S. ca++−11.9 mg/dl (8.5–10.5). Skeletal survey for myeloma was negative. Serum PTH, Vitamin D, and protein electrophoresis were normal. In view of possible paraneoplastic syndrome, positron emission tomography–computed tomography (CT) revealed multiple enlarged metabolically active mediastinal, bilateral hilar, and prehilar lymph nodes [Figure 1] and [Figure 2]. Several soft-tissue density metabolically active nodules diffusely distributed in bilateral lung fields were also present. CT-guided biopsy of mediastinal lymph nodes showed noncaseating granulomas with multinucleate cells [Figure 3] and [Figure 4]. Bronchoalveolar lavage (BAL) was negative for malignant cells. Tuberculosis (TB) PCR was done in BAL, and the biopsy tissue was negative. Mantoux and TB quantiferon gold were negative. S. ACE level was 96U/L (10–70). The diagnosis of sarcoidosis was made. Retrospective evaluation of the other organ involvement was negative (especially skin and eye). He was treated with methylprednisolone 1 g pulse for 3 doses, followed by 1 mg per kg body weight and tapered 5 mg every 2 weeks. Hydroxychloroquine and azathioprine were used as steroid-sparing agents. He recovered completely in 4-week duration and is on follow-up for the last 2 years without relapse of the disease and is now only on HCQS the comparison of the investigations before and after treatment have been given in [Table 1].
|Figure 1: PET CT revealing uptake in pre-tracheal and paraaortic lymph nodes|
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|Figure 3: Lymph node biopsy revealing non caseating granulomatous lesions|
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|Figure 4: Higher power microscopic picture of lymph node biopsy revealing non caseating granuloma with multinucleate giant cells|
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|Table 1: Investigations before and after treatment (treatment started from 15th February)|
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| Discussion|| |
In sarcoidosis, neurological manifestations often manifest along with extra neurological involvement in the form of hilar adenopathy and raised angiotensin-converting enzyme levels. Neurological manifestations usually occur in the initial 2 years of illness. Although the manifestations can be protean, cranial neuropathies are most common, followed by optic neuropathy and endocrinal/hypothalamic–pituitary dysfunction. Peripheral neuropathy may occur in 4%–20% of the cases., Updated consensus NS diagnostic criteria were published in 2018. This was to categorize patients based on diagnostic certainty into definite, probable, and possible NS based on pathologic and clinical features, emphasizing clinical phenotype, and biopsy confirmation [Table 2]. Our case falls in the probable category as the tissue diagnosis is from extraneuronal tissue.
|Table 2: Clinical criteria for a diagnosis of neurosarcoidosis (2018 neurosarcoidosis consortium consensus)|
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Symmetric chronic sensorimotor neuropathy with axonal features on nerve conduction studies is reported to be the most common noncranial nerve peripheral neuropathy. Guillain–Barre-like syndrome, large and small fiber polyneuropathies, or polyradiculoneuropathy with pure motor, sensory, or mixed sensorimotor features are other manifestations of peripheral nervous system sarcoidosis. Histopathological evidence from nerve and muscle increases the diagnostic yield. Subclinical muscle involvement has been described in up to 90% of nerve biopsies. GBS often presents with acute flaccid paralysis along with areflexia, albumin-cytological dissociation, and demyelinating disease on the nerve conduction study. Miller Fisher syndrome (MFS) is a rare variant of GBS and usually presents with at least two of the following features: ataxia, areflexia, and ophthalmoplegia. MFS is commonly associated with the involvement of the lower cranial and facial nerves. A protracted course beyond 4 weeks requires further evaluation for other causes. Small fiber neuropathy, fatigue, and cognitive failure in association with systemic sarcoidosis are conceptualized as a paraneurosarcoidosis wherein the symptoms are sequelae not related to granulomatous involvement and the nerve conduction studies is normal., Intrathecal inflammation in NS is reflected in CSF analysis and is necessary in excluding alternative etiologies, especially in the presence of leptomeningeal enhancement on MRI. Although CSF analysis in NS lacks specificity, mild-to-moderate (lymphocyte predominant) pleocytosis (usually <100 cells/μL) along with CSF protein elevation (which may be in isolation) can be a marker of inflammation. Leptomeningitis which may be seen in NS is characterized by the presence of hypoglycorrhachia (also seen in TB, malignancies, and fungal infection). Oligoclonal bands, elevated IgG, and elevated ACE levels have poor sensitivity and specificity for NS. CSF studies can also be helpful to monitor for NS disease activity over time, such as in response to treatment, particularly opening pressure, cell count, total protein, glucose, IgG index, and oligoclonal band.
MRI with and without gadolinium is the most appropriate imaging modality in suspected. Gadolinium enhancement lacks specificity, but is a helpful marker of active NS. Deep medullary vein engorgement and radial perivenular enhancement have also been described in NS. MRI has value as a biomarker for response to therapy and critically informs clinical decision-making. The therapy remains controversial due to the lack of randomized controlled trials in NS.
Glucocorticoids remain the first-line therapy for NS.,, Patients with severe presentations may require pulse-dose IV methylprednisolone, 1 g daily for 3–5 days, followed by a prolonged oral glucocorticoid taper. For less severe presentations, prednisone 0.5–1 mg/kg/d or bioequivalent doses in other glucocorticoid formulations may be effective. A meta-analysis from 2016 noted a favorable outcome with glucocorticoids in 71% of patients with NS. Azathioprine, methotrexate, mycophenolate mofetil, hydroxychloroquine, cyclophosphamide, and TNF inhibitors have been used as steroid-sparing agents in NS. In a retrospective study of 234 patients with NS noted a lower risk for relapse in patients treated with methotrexate, cyclophosphamide, or infliximab than with mycophenolate. Azathioprine has also been used as a treatment for sarcoidosis with varying effectiveness., Hydroxychloroquine has been particularly useful in cutaneous disease, hypercalcemia, and in some cases of NS.,, There are only few case reports of NS presenting as GBS that have been described [Table 3]. The outcome of these has varied from complete recovery to death.,,
|Table 3: Comparisons of the case reports of neurosarcoidosis with Guillian-Barre syndrome-like presentation|
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| Conclusion|| |
GBS-like presentation is a rarer manifestation of NS especially when the presentation is atypical and/or is associated with extra-neurological manifestations with CSF pleocytosis. Unlike idiopathic GBS, NS responds well to steroids and second-line agents depending on the severity of the disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]