Post Scrotal Tap Morvan’s Syndrome with Nephrotic Syndrome

Sir, Morvan’s syndrome is a male-dominated autoimmune disorder with symptoms of peripheral nerve hyperexcitability, autonomic dysfuncion, and central manifestations. It is thought to be related to the formation of antibodies against voltage-gated potassium channel and approximately half of the cases are associated with underlying thymoma.[1] Neuromyotonia and MoS have been described in Indian context after an exposure to indigenous medicines[2] and after scrotal tapping and instillation of chemicals into the scrotal sac for the treatment of hydrocele.[3] Nephrotic syndrome is the combination of heavy proteinuria, hypoalbuminemia and edema. It can result from the deposition of immune-complexes in renal glomerulus.[4] Here, we are reporting a patient with the features of both MoS with antibodies to VGKC complex in serum and nephrotic syndrome with PLA2R antibody deposition in glomeruli. A32-year-old male presented with pain and cramps in both lower limbs for 1.5months, followed by insomnia for 15 days, associated with excessive sweating and excessive cold perception. He also developed facial puffiness and lower limb edema for three weeks duration. He had a history of scrotal fluid tapping for hydrocele and instillation of some unknown sclerosing agent into the scrotal sac four months back. On neurological examination, the patient was conscious, irritable, power - 5/5 in all four limbs, DTR ++ in all limbs, planters –flexor bilaterally with hyperalgesia in both feet. He had continuous rippling of calf muscles on the left side and also intermittent fasciculations in right calf along with tremors in left foot. The MRI of lumbosacral spine was normal and NCV done in both lower limbs was normal. EMG of left gastrocnemius revealed the evidence of peripheral nerve hyperexcitability in the form of abnormal spontaneous activity, including doublet, triplets, and muliplets of fasciculations firing at very high intra-burst frequency of around 100Hz [Figures 1 and 2]. His serum sample was positive for CASPR-2/VGKC complex antibodies. His serum urea/creatinine and electrolytes were normal. His spot urine protein creatinine ratio was 6.1(nephrotic range proteinuria). Renal biopsy showed the membranous pattern of glomerulopathy (MGN) in all glomeruli with no evidence of chronicity and IFTA (interstitial fibrosis and tubular atrophy) and DIF (direct immunofluorescence) studies showed strong positivity for anti-PLA2R antibodies in glomerular mesangium. The patient was given pulse steroid therapy and symptomatic treatment with antiepileptics and his symptoms subsided over the next two weeks.Figure 1: EMG left gastrocnemius showing abnormal spontaneous activity in the form of doublet fasciculationsFigure 2: EMG left gastrocnemius showing abnormal spontaneous activity in the form of triplet fasciculations firing at the intra-burst frequency of 100 HzIn 1890, the French physician Dr. Augustin Marie Morvan first described this neurological syndrome and called it “la choree fibrillaire”. MoS is predominantly a male dominant entity with a male to female ratio of 19:1.[1] The symptoms of peripheral nerve hyperexcitability are often the presenting features with neuromyotonia seen in all the cases[1] often associated with neuropathic pain.[5]Autonomic dysfunction, commonly presents as hyperhidrosis, tachycardia, arrhythmia, and urinary dysfunction. Central features include hallucinations, confusion and amnesia with marked insomnia reported in about 89% of patients.[5] The elevated levels of VGKC complex antibodies are found in 45% of patients.[1]They usually have high levels of CASPR2 antibodies, although LGI-1 antibodies may also be seen in a few patients.[5]Thymoma is associated in 40% of cases and CASPR-2positive patients are more likely to harbor thymoma.[6] Other tumours associated with MoS include adenocarcinoma of lung, in situ sigmoid carcinoma and prostate adenoma.[7] Acetylcholine receptor antibodies are seen in 30% of patients, but the clinical features of myasthenia gravis are seen in only 10% of cases.[1] A thorough search for malignancy is also recommended at the time of diagnosis.[6] Needle EMG in MoS shows the evidence of peripheral nerve hyperexcitability in the form of fasciculations (doublets, triplets, and multiplets) and myokymic and neuromyotonic discharges.[6] Pangariya et al.[2] have described a series of 20 patients from Northwest India with acquired neuromyotonia and some of their patients also had central features. Most of these patients received indigenous medication for more than a month. Sharma et al. reported the post scrotal tap MoS.[3,8] These patients developed the features of MoS after instillation of various sclerosing agents into the scrotal sac for treatment of hydrocele. These chemicals included lignocaine, denatured spirit, ceftriaxone, and mercury powder.[3,8] The symptoms were seen after a median interval of 1.5–3 months. Our patient also belongs to the similar geographical region and developed these symptoms after about 2.5months of scrotal tapping and instillation of some unknown chemical. They postulated the instillation of chemicals into scrotal sac and consequent inflammatory response may break the immune tolerance and might trigger antibody formation against voltage-gated potassium channels.[8] Nephrotic syndrome is caused by increased permeability through the damaged basement membrane in renal glomeruli. Causes include primary kidney diseases, such as minimal change disease, focal segmental glomerulosclerosis and membranous glomerulonephritis and secondary injury with diabetes, amyloidosis and systemic lupus erythematosus.[4] However, the most common cause of nephrotic syndrome in adults is membranous nephropathy and results from either immune complex deposition from circulation or in situ formation of these immune complexes.[4] Autoantibodies against M-type phospholipase A2 receptor (PLA2R) are found in about 70% of patients with membranous glomerulonephropathy.[9] The autoimmune basis for the pathogenesis of MoS has been suggested based on the presence of VGKC complex antibodies and its frequent occurrence in association with thymoma and ACh receptor antibodies.[1] A case of MoS in association with thymoma and systemic lupus erythematosus has also been described.[10] To our knowledge this is the first case in literature describing the association of MoS with nephrotic syndrome which is also an autoimmune entity. This may be due to the incidental cooccurance of Morvan’s syndrome after scrotal tapping and sclerosing agent instillation in a patient of membranous nephropathy. However this could also be a case of poly autoimmunity that is the co-occurance of two or more autoimmune diseases in a single patient. Polyautoimmunity is thought to be due to the similar genetic background shared by different autoimmune diseases.[11] About 25% of patients with autoimmune diseases have a tendency to develop additional autoimmune diseases.[12] Our case report emphasizes the fact that patients with MoS may also have associated autoimmune disorders targeting organ systems other than CNS & PNS. 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.