Papilledema Unravelling a Sinister Neuropathy: A Rare Scenario
Year: 2025
Type: article
Abstract: Sir, A 45-year-old lady presented to the ophthalmology department with insidious onset progressive diminution of vision in both eyes for 2–3 months. She had transient visual obscurations (TVOs) with postural changes without accompanying headache or double vision. She had a visual acuity of 6/12 in both eyes with bilateral grade 4 papilledema. Visual field analysis showed an enlarged blind spot with no evidence of other cranial nerve deficits. Increased intracranial pressure secondary to space occupying lesion, cerebral venous thrombosis, or idiopathic intracranial hypertension (IIH) were considered, but the absence of headache was unusual. MRI brain was done, which showed dilated optic nerve sheaths with tortuosity and partial empty sella supporting the diagnosis of IIH, and the patient was referred to the neurology department for further evaluation. Her past history was significant for acute onset weakness and numbness of both legs 1 year back. This was diagnosed as Guillain Barre syndrome at another hospital, and she received treatment with intravenous immunoglobulin (IVIG). However, there was no improvement in weakness or numbness. Over the next 6 months, the lower limb weakness remained persistent. Additionally, she developed low backache with pain in both lower limbs and significant weight loss. General physical examination showed an emaciated patient with pedal edema and no significant lymphadenopathy. The abdomen showed hepatosplenomegaly with no free fluid. Motor system examination was normal in upper limbs, while in the lower limbs, the hip and knee power was 4/5 with weakness of both ankle flexion and extension (power 2/5). Deep tendon jerks were absent in legs, and she had high steppage gait. There was reduced touch and pinprick sensation below the knee with impaired vibration and proprioception, suggesting symmetrical, uniform, and length-dependent neuropathy. Romberg was positive. Neurolymphomatosis by direct infiltration or a paraneoplastic neuropathy was considered in view of hepatosplenomegaly. Peripheral neuropathy in association with lymphoma often tends to be subacute or chronic. Sensorimotor multiple mononeuropathies or polyneuropathy can rarely be the initial manifestation as in this patient.[1] Optic nerve infiltration by lymphoma may cause papilledema and visual loss but is associated usually with headache and other cranial nerve deficits. A solid organ disseminated malignancy may cause these findings, but the indolent nature of the illness lasting for more than a year without any cough, melena, hemoptysis, breast lump, and so on makes it less likely. POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) was a strong consideration with an indolent, slowly progressive peripheral neuropathy accompanied by organomegaly and papilledema. Investigations revealed a normal hemogram and biochemical parameters, but total protein was decreased (5.8 gm/dl) with albumin of 3.4 g/dl, globulin of 2.4 g/dl, and a preserved albumin/globulin (A/G) ratio of 1.4. Nerve conduction study showed demyelinating sensorimotor polyradiculoneuropathy involving the upper limbs with inelicitable motor and sensory nerve action potentials in the lower limbs (demyelination with secondary axonal loss) [Table 1]. Lumbar puncture was done. The opening pressure was normal (16 cm H2O), with cerebrospinal fluid analysis showing elevated protein (183 mg/dl), normal sugars (80 mg/dl), and cells (1 lymphocyte/mm3) with negative malignant cytology.Table 1: Nerve conduction study dataSerum electrophoresis showed M band (0.4 g/dl) in the gamma globulin region, and immunofixation showed elevated free kappa and lambda light chains with a preserved kappa lambda ratio. CT (computed tomography) chest was normal; CT abdomen showed hepatosplenomegaly (liver 22 cm, spleen 15 cm) and a lytic lesion in the right sacral ala measuring 5 × 3 × 5 cm with cortical erosions and irregularities. The patient subsequently underwent whole body PET-CT (positron emission tomography–computed tomography), which showed a large metabolically active lytic lesion in the right sacrum. The patient was thus diagnosed with POEMS syndrome and was referred to an oncologist for further management. Bone marrow aspiration and biopsy showed an increase in plasma cells, while biopsy from the lesion suggested plasma cell neoplasm. POEMS syndrome is an uncommon paraneoplastic disorder related to a very rare plasma cell neoplasm. The accumulation of light chains produced by the abnormal plasma cells and the concomitant elevated VEGF (vascular endothelial growth factor) levels account for the various manifestations of the disease. The latest diagnostic criteria require both mandatory criteria, one major criterion and one minor criterion for confirmation.[2] Both mandatory major criteria (polyneuropathy and monoclonal plasma cell disorder) and one major criterion (bone lesions) were met by the patient. Organomegaly, extravascular volume overload, and papilledema were the minor criteria observed in our patient. Peripheral neuropathy is commonly the presenting manifestation of POEMS, but often, the diagnosis is missed with ensuing treatment delays. The electrophysiological studies show a demyelinating polyradiculoneuropathy, and the patient is usually treated as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which fails to produce a satisfactory response. Neuropathy in POEMS syndrome can be electrophysiologically differentiated from other demyelinating neuropathies like CIDP by the predominant affection of the intermediate nerve segment characterized by relatively less prolonged distal latencies and disproportionately prolonged F latencies with a higher terminal latency index (TLI).[3] The TLI is measured as distal nerve conduction distance/(proximal motor conduction velocity x distal motor latency), and a value more than >0.35 suggests preferential involvement of proximal nerve segments as compared to distal nerve terminals.[4] The TLI was 0.39 and 0.48 in the right and left median nerves in the patient, respectively. In contrast to CIDP, there is uniform demyelination without conduction blocks in POEMS and the discrepancy between upper and lower limb conduction tends to be more pronounced. These features were confirmed in the patient’s nerve conduction study. It was the evaluation of papilledema that led to the eventual diagnosis of POEMS syndrome in the patient. In a study done at Mayo clinic, about 52% of poems patients had papilledema with 29% being asymptomatic at the first ocular examination.[5] Insidious onset of visual impairment with TVOs, papilledema, and radiological (MRI brain) features suggested a possibility of IIH, but the absence of headache, weight loss, peripheral neuropathy, and the normal CSF pressures with a high CSF protein hinted an alternate etiology. Increased vascular permeability secondary to elevated VEGF and elevated CSF protein may account for papilledema in POEMS as in other inflammatory polyneuropathies. Diagnosing POEMS syndrome in the early stages may be challenging and difficult, but a thorough general physical examination and awareness of the unique electrophysiological features of peripheral neuropathy in POEMS may prove rewarding. The disease responds well to the current treatment modalities, and an early diagnosis results in a favorable outcome, while diagnostic delays are associated with worse outcomes. Papilledema is well documented in POEMS, but the presentation as visual impairment is only rarely encountered in clinical practice. POEMS syndrome should be an important consideration in patients who have coexisting papilledema and peripheral neuropathy (current or recent past). All cases of papilledema with normal MRI brain (except for signs of raised intracranial pressure) require a mandatory lumbar puncture analysis to identify the exact underlying etiology. 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. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Neurology India
Authors: Jomal Mathew Chittilappilly, Dona Anne Mathew
Institution: Little Flower Hospital & Research Centre
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4409499067