Asian Journal of Transfusion Science
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CASE REPORT Table of Contents   
Year : 2023  |  Volume : 17  |  Issue : 1  |  Page : 117-120
Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome

1 Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurological Science, Post Graduate Institute of Medical Education and Research, Chandigarh, India

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Date of Submission05-Jul-2021
Date of Decision04-Sep-2021
Date of Acceptance14-Jan-2022
Date of Web Publication12-Dec-2022


Isaacs syndrome is a disease characterized by nerve hyperexcitability and pseudomyotonia and treated with immunomodulatory and symptomatic therapy approaches. Here, we report a case of anti-(leucine-rich glioma-inactivated 1) antibody-positive patient diagnosed as Isaacs syndrome and accomplished a nearly complete response to only four sessions of therapeutic plasma exchange (TPE). Our experience suggests that TPE along with other immunomodulatory agents may be beneficial and well-tolerated approach in patient with Isaacs syndrome.

Keywords: Antibodies against voltage-gated potassium channel, electromyogram, therapeutic plasma exchange

How to cite this article:
Tripathi PP, Kumari S, Prabhat N, Lamba DS, Hans R, Goyal MK, Lal V, Sharma RR. Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome. Asian J Transfus Sci 2023;17:117-20

How to cite this URL:
Tripathi PP, Kumari S, Prabhat N, Lamba DS, Hans R, Goyal MK, Lal V, Sharma RR. Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome. Asian J Transfus Sci [serial online] 2023 [cited 2023 Mar 27];17:117-20. Available from:

   Introduction and Case Report Top

Isaacs syndrome is a rare humorally mediated autoimmune neuromuscular disorder, characterized by continuous twitching of muscles at rest, diminished reflexes, progressive muscle stiffness, and neuromyotonia with a prevalence of <1/1,000,000 usually affecting people between 15 and 60 years of age.[1],[2],[3] It primarily involves peripheral nerves with blockade of the outward going potassium current and formation of antibodies against voltage-gated potassium channels (Anti-VGKC).[4] This forms the basis of treatment and utilization of plasma exchange for short-term relief and reduction of neuromyotonia.[5],[6],[7] We report a case of a 17-year-old male, who presented with a history of pain in both legs, especially calf muscles for 10 months followed by a burning sensation in the dorsum of the foot for 6 months (1–2 times/day for 6 months duration). He was treated at outside local hospital with conservative approach including pain-relieving agents (tablet acelofenac SR 100 mg two times a day/ Si opus sit (SOS)), antiepileptics (tablet phenytoin 100 mg two times a day for 2 weeks), and multivitamins (tablet neurobion forte, once a day for 1 month). His condition worsened for the past 2 months, and he had generalized body aches, muscle stiffness, excessive sweating, and continuous twitching of muscles with 5–6 episodes/day of symptoms, over a span of 30 min, mostly in the evening time, and extend to such a degree that he had to take analgesics to relieve symptoms. Symptoms worsened further and progressed to pinprick sensation (paresthesia and dysesthesia) in both the soles of the foot with excessive foul-smelling sweating (5–6 episodes/day). He also complained of insomnia (3 times/week for the past 3 months), continuous twitching of muscle sensation (5–6 times/day for the past 1 month) along with myokymia (2–3 episodes/day), all over the body, and tremors in both hands in resting position. Complete hemogram and other routine investigations were within normal limits except anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (positive) and electromyogram (EMG) which revealed a neurogenic hyperexcitability pattern. Other autoimmune panel antibodies such as contactin-associated protein-2 (Caspr2) were negative. Based on clinical history, antibody testing, and the EMG pattern, the diagnosis of Isaacs syndrome was made. As a part of the treatment protocol for this patient, a call for therapeutic plasma exchange (TPE) was received in the Department of Transfusion Medicine. After an initial assessment, plasma exchange for this patient was started on every alternate day from the next day of admission. The estimated total blood volume of the patient was 3900 ml with a weight of 60 kg and the mean plasma volume was 2184 ± 27.57 ml. On average, 2207 ± 28 ml of plasma (1–1.5 plasma volume) was exchanged using an Optia® Spectra automated cell separator (Terumo BCT, Lakewood, Co) using 5% human serum albumin and 0.9% normal saline as replacement fluid (70% and 30%, respectively[8]) with both peripheral vein line catheter access. Injection calcium gluconate (1%) was given throughout all procedures with separate venous line and in addition to replacement fluids. The patient was monitored throughout all procedures for any signs of adverse effects. The patient's details and procedural parameters details are shown in [Table 1]. Along with plasma exchange, pulse therapy of intravenous methylprednisolone (1 mg/kg/day for 5 days) and antiepileptic drugs (phenytoin 100 mg BID and gabapentin 400 mg BID) were also started. The patient was discharged after 10 days of hospital admission and on regular follow-up.
Table 1: Detailed plasma exchange sessions

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Effectiveness of therapeutic plasma exchange with follows up

Marked improvement was seen after each plasma exchange. There was immediate remission of pain and muscle twitches after the first plasma exchange session. The degree and frequency of resting myokymia, generalized body ache, and hyperhidrosis were on decreasing trend after each plasma exchange and disappeared after 4th plasma exchange. The patient was on improving trend with decreased in pain sensation and contracting muscle sensation at the end of all plasma exchange sessions as the patient did not require any pain-relieving medications after the first plasma exchange. The patient was discharged after four procedures. At 3 months of follow-up, there was a significant clinical improvement (including the absence of neuromyotonia, generalized body aches, insomnia, and reduction in muscle twitching and stiffness) and at 6-month follow-up, there were no symptoms of any illness and the patient was able to do his normal routine daily work. At present, he is on a tapering dose of phenytoin and gabapentin with normal blood counts and liver function tests.

   Discussion and Conclusion Top

Isaacs' syndrome present with peripheral nerve hyperexcitability phenomenon in which there is a shift of resting membrane potential towards lesser negative values leads to exponential the firing of neurons in the peripheral nervous system.[9] This syndrome is a humoral mediated dendrotoxin-sensitive fast potassium channelopathy. Studies reported approximately 35% of cases with anti-VGKC.[9],[10] These antibodies decrease the density of functional VGKCs, which further lead to an increase in the expression of sodium channels and decrease in out flux of the potassium channel, contributing to neuron sensitivity to neuroexcitability and ectopic discharges. Literature mentioned that those other antibodies causing Isaacs syndrome include antibodies directed against LGI1 (as in our case), Caspr2, and other unknown proteins that form a complex with VGKC. These antibodies are against protein complexes to potassium channels instead of the whole channel by itself.[9],[10],[11] Continuous contraction or twitching of muscles are pathological features in Isaacs' syndrome related to autoimmune complexes. TPE is an effective line of treatment for these patients as TPE results in the removal of pathogenic material as reported in the literature.[5],[12] Treatment options due to fewer incidence of VGKC-complex antibody-associated diseases are limited.[11] Steroids are basic drugs along with any combination therapy. According to the American Society for Apheresis 2019, TPE for VGKC antibodies comes under category II 1(B).[13] Reported cases in literature with VGKC antibodies are very few to date (<100 cases). Vincent et al. (2004) reported complete resolution of symptoms in 4 out of 7 patients in VGKC antibodies positive patients where TPE was administered in conjunction with steroids and intravenous immunoglobulin. Almost similar results were shown by Jaben and Winters with the effective use of plasma exchanges.[15] Another study by Skeie et al. mentioned that effective clinical improvement lasting about 6 weeks with a fall in VGKC antibody titers and reduction in electromyography can be often produced by TPEs.[7],[14] Studies mentioning the effectiveness of TPE are mentioned in [Table 2].[5],[9],[15],[16],[17],[18] In addition, pulse therapy and antiepileptic drugs might have adjuvant effects with TPE. Clearance rate of these drugs is very less with plasma exchanges due to less protein binding and extravascular distribution.[19] To the best of our knowledge, this is the first case reported in the literature from North India with significant clinical benefit from TPE. More cases have to be reported for establishing the therapeutic role TPE in neurological conditions like Isaacs syndrome along with other immunomodulation therapy.
Table 2: Literature review in patients with Isaacs syndrome treated with plasma exchange or immunoadsorption plasmapheresis or plasmapheresis or intravenous immunoglobuli

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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.

   References Top

Isaacs H. Continuous muscle fibre activity in an Indian male with additional evidence of terminal motor fibre abnormality. J Neurol Neurosurg Psychiatry 1967;30:126-33.  Back to cited text no. 1
Isaacs H. A syndrome of continuous muscle-fibre activity. J Neurol Neurosurg Psychiatry 1961;24:319-25.  Back to cited text no. 2
Panagariya A, Kumar H, Mathew V, Sharma B. Neuromyotonia: Clinical profile of twenty cases from northwest India. Neurol India 2006;54:382-6.  Back to cited text no. 3
[PUBMED]  [Full text]  
Saeed AA, Saeed Rabeen R, Mohammed ZA, Hamid SF. A 72-year-old man with Isaacs' syndrome: A rare entity with different outcomes. World J Neurosci 2016;6:82-4.  Back to cited text no. 4
Ishii A, Hayashi A, Ohkoshi N, Oguni E, Maeda M, Ueda Y, et al. Clinical evaluation of plasma exchange and high dose intravenous immunoglobulin in a patient with Isaacs' syndrome. J Neurol Neurosurg Psychiatry 1994;57:840-2.  Back to cited text no. 5
Sinha S, Newsom-Davis J, Mills K, Byrne N, Lang B, Vincent A. Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome) Lancet 1991;338:75-7.  Back to cited text no. 6
Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review. Brain 1993;116:453-69.  Back to cited text no. 7
Hans R, Sharma RR, Marwaha N, Suri D, Kumar R, Gupta A, et al. Efficacy and safety of therapeutic plasma exchange by using apheresis devices in pediatric atypical hemolytic uremic syndrome patients. J Clin Apher 2016;31:381-7.  Back to cited text no. 8
Bin Waqar SH. Waves in extremities: A rare report of isolated Isaacs' syndrome. Cureus 2019;11:e4687.  Back to cited text no. 9
Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;125:1887-95.  Back to cited text no. 10
Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain 2010;133:2734-48.  Back to cited text no. 11
Das J, Tan M, Rachael M, James BL, David G, Nazar S. Therapeutic plasma exchange for neurological disorders associated with anti-VGKC antibodies. J Neurol Neurosurg Psychiatry 2017;88 Suppl 1:A1-83.  Back to cited text no. 12
Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al. Guidelines on the use of therapeutic apheresis in clinical practice – Evidence-based approach from the Writing Committee of the American Society for Apheresis: The eighth special issue. J Clin Apher 2019;34:171-354.  Back to cited text no. 13
Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I, Harms L, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 2010;17:893-902.  Back to cited text no. 14
Jaben EA, Winters JL. Plasma exchange as a therapeutic option in patients with neurologic symptoms due to antibodies to voltage-gated potassium channels: A report of five cases and review of the literature. J Clin Apher 2012;27:267-73.  Back to cited text no. 15
Orsucci D, Cafforio G, Moscato G, Napolitano A, Margelli M, Mazzoni M. Steroids and plasma exchange in Isaacs' syndrome with anti-Caspr2 antibodies. Neuroimmunol Neuroinflammation 2018;5:7.  Back to cited text no. 16
Ibrahim I, Abdelzahir D, Mostafa A, Mansour O. Neuromyotonia (Isaacs' Syndrome) in a patient with shistosomaiasis with good response to plasmapharesis: A case report. Internet J Intern Med 2013;2:10-4.  Back to cited text no. 17
Nakatsuji Y, Kaido M, Sugai F, Nakamori M, Abe K, Watanabe O, et al. Isaacs' syndrome successfully treated by immunoadsorption plasmapheresis. Acta Neurol Scand 2000;102:271-3.  Back to cited text no. 18
Cheng CW, Hendrickson JE, Tormey CA, Sidhu D. Therapeutic plasma exchange and its impact on drug levels: An ACLPS critical review. Am J Clin Pathol 2017;148:190-8.  Back to cited text no. 19

Correspondence Address:
Ratti Ram Sharma
Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh Sector-12, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_88_21

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