Paraneoplastic neuropathies and peripheral nerve hyperexcitability disorders.

Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.

Paraneoplastic autoimmune neurologic disorders associated with thymoma.

Thymoma is often associated with paraneoplastic neurologic diseases. Neural autoantibody testing is an important tool aiding diagnosis of thymoma and its autoimmune neurologic complications. Autoantibodies specific for muscle striational antigens and ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily are the most prevalent biomarkers. The autoimmune neurologic disorders associating most commonly with thymoma are myasthenia gravis (MG), peripheral nerve hyperexcitability (neuromyotonia and Morvan syndrome), dysautonomia, and encephalitis. Patients presenting with these neurologic disorders should be screened for thymoma at diagnosis. Although they can cause profound disability, they usually respond to immunotherapy and treatment of the thymoma. Worsening of the neurologic disorder following surgical removal of a thymoma may herald tumor recurrence. Prompt recognition of paraneoplastic neurologic disorders is critical for patient management. A multidisciplinary approach is required for optimal management of neurologic autoimmunity associated with thymoma.

Ocular neuromyotonia: an unusual case after radiotheraphy for nasopharyngeal carcinoma.

Ocular neuromyotonia (ONM) is an infrequent disorder characterised by recurrent episodes of binocular diplopia caused by paroxysmal contraction of one or several extraocular muscles innervated by the same cranial nerve. It can be triggered spontaneously or caused by prolonged contraction of specific eye muscle(s) and is usually related to a local intracranial radiotherapy antecedent. We report the case of a 46-year-old woman who developed intermittent episodes of binocular diplopia eight years after radiotherapy for a nasopharyngeal carcinoma. After a complete neuro-ophthalmic assessment we diagnosed the case as an abducens nerve neuromyotonia. Although it is infrequent, radiotherapy to the nasopharynx is a possible cause of ONM, due to the proximity to the base of the skull and extraocular motor nerve pathways, especially that of the VI cranial nerve, as is the case presented in this article, about a patient whose history is a nasopharyngeal carcinoma treated with local radiotherapy.

Systematic Review of the Clinical Characteristics and Management of Isaac Syndrome.

OBJECTIVES: Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies. RESULTS: We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases). CONCLUSIONS: IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.

Occult bowel cancer presenting as Morvan syndrome.

A man in his mid-60s presented with a 3-month history of progressive muscle twitching, agitation, cognitive impairment, insomnia, hyperhidrosis and lower limb pain. He had fasciculations, myokymia, myoclonus, exaggerated startle response and significant postural hypotension. Electrophysiological studies showed evidence of peripheral nerve hyperexcitability with neuromyotonia. Contactin-associated protein-like 2 antibodies (CASPR2) were strongly positive. A diagnosis of Morvan syndrome was made. CT of the chest, abdomen and pelvis was undertaken to identify any occult malignancy, and a large bowel carcinoma in situ was identified and resected. His central nervous system and autonomic symptoms significantly improved following surgery, but neuromyotonia persisted, and this was treated with intravenous immunoglobulins and steroids. Early detection of bowel cancer in this patient enabled curative treatment.

Isaacs syndrome with LGI1 and CASPR2 antibodies after HPV vaccination: A case report.

RATIONALE: Isaacs syndrome is peripheral nerve hyperexcitability characterized by spontaneous muscle twitching and rigidity and is often associated with antibodies to CASPR2 (contactin-associated protein-like 2) and LGI1 (leucine-rich glioma-inactivated 1). But it is a rare Isaacs syndrome with LGI1 and CASPR2 antibodies after human papilloma virus (HPV) vaccination. PATIENT CONCERNS: The patient presented with limb pain, muscle twitching, numbness in the extremities and around the mouth, and hand rash after the second dose of HPV vaccine. DIAGNOSES: Laboratory tests indicated positive for LGI1 antibodies, CASPR2 antibodies, anti-phosphatidylserine/prothrombin antibodies and anti-sulfatide antibodies, TPO and ATG, IgG E. The patient post-M-wave discharges were seen on F-wave examination of the posterior tibial nerve in both lower limbs. We diagnosis the patient with Isaacs syndrome. INTERVENTIONS: Treatment with the intravenous immunoglobulin (IVIG) treatment, after 5 days of IVIG therapy (0.4 mg/kg/day), the rash on the hand disappeared, the pain was relieved, the sleep improved. OUTCOMES: After 3 Courses of treatment, the clinical manifestations of the nervous system disappeared and negative responsibility antibodies profile. LESSONS: This case report suggests a possible adverse reaction to HPV vaccination, which could be treated by attempting several periods of IVIG therapy. The underlying immune mechanisms need to be studied with further extensive data.

Clinical, neurophysiological and serological clues for the diagnosis of neuromyotonia and distinction from cramp-fasciculation syndrome.

Neuromyotonia and cramp-fasciculation syndrome diagnosis currently relies on neurophysiological examination. In this study we investigated the clinical features and neural antibody profile of patients with neuromyotonia and cramp-fasciculation syndrome to assess the diagnostic value of serological testing. Available sera from adult patients with electromyography-defined neuromyotonia and cramp-fasciculation syndrome were tested for neural antibodies by indirect immunofluorescence on mouse brain sections and live cell-based assays. Forty patients were included, 14 with neuromyotonia and 26 with cramp-fasciculation syndrome. Neural antibodies were detected in 10/10 neuromyotonia sera, most commonly against contactin-associated protein 2 (7/10, 70%), and in 1/20 (5%) cramp-fasciculation syndrome sera. Clinical myokymia, hyperhidrosis, and paresthesia or neuropathic pain were more common in neuromyotonia and mostly associated with contactin-associated protein 2 antibodies. Central nervous system involvement was present in 4/14 (29%) neuromyotonia patients. A tumor was detected in 13/14 (93%) neuromyotonia patients (thymoma, 13), and in 4/26 (15%) with cramp-fasciculation syndrome (thymoma, 1; other neoplasms, 3). Twenty-one/27 (78%) patients achieved a significant improvement or complete remission. Our findings highlight clinical, neurophysiological and serological clues that can be useful in the diagnosis of neuromyotonia and cramp-fasciculation syndrome. Antibody testing is valuable for neuromyotonia diagnosis, while its usefulness in cramp-fasciculation syndrome confirmation is limited.

Leucine-rich Glioma-inactivated 1 Encephalitis Followed by Isaacs Syndrome: Alternating Presence of Pathogenic Autoantibodies to Leucine-rich Glioma-inactivated 1 and Contactin-associated Protein-like 2.

The coexistence of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) autoantibodies in the same individual is surprisingly often observed. We herein report the first case of LGI1 encephalitis followed by Isaacs syndrome in which LGI1 and CASPR2 antibodies in the serum and cerebrospinal fluid (CSF) were measured during the entire disease course. After the resolution of limbic encephalitis, LGI1 antibodies disappeared from the CSF simultaneously with the appearance of CASPR2 antibodies in the serum. The alternating presence of these pathogenic autoantibodies along with the clinical and phenotypic alternations suggested that LGI1 encephalitis was associated with CASPR2 autoantibody production in the peripheral tissue, leading to CASPR2-associated Isaacs syndrome.

Ocular neuromyotonia: a review of diagnosis and treatment.

PURPOSE OF REVIEW: The current review will cover the clinical presentation, causes, epidemiology, differential diagnoses, workup, and treatment of ocular neuromyotonia (ONM) in detail. RECENT FINDINGS: While ONM largely remains a unilateral eye movement disease affecting adults with a history of sellar radiation, recent case reports highlight an expansion of this presentation to include bilateral, pediatric, and congenital cases. SUMMARY: ONM is a rare but recognizable ocular motility disorder involving sustained contraction of the extraocular muscle, commonly resulting in intermittent diplopia. Diagnosis of ONM relies upon a thorough history and clinical exam, with particular attention to history of radiotherapy and eccentric gaze testing. Treatment with carbamazepine remains first-line therapy, although other membrane stabilizing agents and surgical interventions can be effective.

Autoimmune neuromyotonia.

PURPOSE OF REVIEW: Autoimmune neuromyotonia encompasses a group of rare immune-mediated neurological disorders frequently associated with anti-contactin-associated protein-like 2 (CASPR2) antibodies and featuring clinical and electrical signs of peripheral nerve hyperexcitability (PNH). We aim to summarize the current knowledge on immune-mediated neuromyotonia, focusing on clinical presentations, pathophysiology, and management. RECENT FINDINGS: Neuromyotonia is a major feature of several autoimmune neurological syndromes characterized by PNH with or without central neurological system involvement. Experimental and clinical evidence suggest that anti-CASPR2 antibodies are directly pathogenic in autoimmune neuromyotonia patients. SUMMARY: Neuromyotonia, a form of PNH, is a major feature in several syndromes associated with anti-CASPR2 antibodies, including cramp-fasciculation syndrome, Isaacs syndrome, Morvan syndrome, and autoimmune limbic encephalitis. Diagnosis relies on the identification of motor, sensory, and autonomic signs of PNH along with other neurological symptoms, anti-CASPR2 antibody-positivity, and of characteristic electroneuromyographic abnormalities. Paraneoplastic associations with thymoma are possible, especially in Morvan syndrome. Patients usually respond to immune-active treatments, including steroids, intravenous immunoglobulins, plasma exchanges, and rituximab.

Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report.

BACKGROUND: HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. CASE PRESENTATION: A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. CONCLUSIONS: Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

Neuromyotonia: a skin-deep problem.

A 45-year-old woman was evaluated for right-sided hemicorporal scar-like skin lesions on her arm and thoracic and inguinal areas that appeared shortly after reduction mammoplasty. Five years later, she developed spontaneous cramps and involuntary abnormal, painful, twitching movements in the same areas. With time, the cramps worsened and disabled the patient. The use of her right arm triggered contractures of muscles and abnormal movements. A diagnosis of neuromyotonia (NMT) was established on the basis of clinical findings and on electromyographic findings of a burst of high-frequency motor unit potentials recorded in the right triceps in the area of skin lesions. The results of medullary, encephalic MRI as well as a comprehensive metabolic panel were normal. She was positive for antinuclear antibodies without specificity. Neither antineural antibodies nor antivoltage-gated potassium channel complex antibodies (specifically, leucine-rich glioma inactivated protein 1 and contactin-associated protein-like-2) were detected. Her skin lesions were diagnosed as morphea. Two combined strategies of treatment were initiated: antiepileptic drugs for NMT and corticosteroids and methotrexate for morphea. NMT is a rare, debilitating neurological complication of morphea.

Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

PURPOSE: To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years. METHODS: Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation. RESULTS: Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to meta-static disease, and one patient has planned follow-up. CONCLUSIONS: Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 2022;59(5):338-343.].

Post-surgical left oculomotor nerve neuromyotonia: Cause or coincidence?

Ocular neuromyotonia (ONM) is characterized by episodes of binocular diplopia usually triggered by an eye movement requiring contraction of the affected extraocular muscle. It consists of an involuntary, sometimes painful contraction of one or more extraocular muscles. It is most often secondary to radiotherapy of the para-sellar region, although other aetiologies have been reported. Some cases do not have a clearly identified aetiology and are classified as idiopathic. Most cases of ONMs are unilateral but bilateral ONMs have also been described.1-4 We report a case of left ONM in a 55-year-old female patient, several weeks after simultaneous surgical resection of two meningiomas, situated on the right side (Simpson II). The particularity of this case is linked to its puzzling presentation, its similarity with spasm of the near reflex and the putative mechanism through which surgery might have precipitated the symptoms.

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies.

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs' syndrome, suggesting that immunotherapy should be considered for Isaacs' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.

Electrodiagnostic Assessment of Hyperexcitable Nerve Disorders.

Peripheral nerve hyperexcitability (PNH) typically presents with complaints of muscle twitching, cramps, and muscle stiffness. Symptoms and signs indicating central and/or autonomic nervous system dysfunction also may be reported. An electroclinical spectrum exists, spanning from the milder cramp-fasciculation syndrome to more severe syndromes characterized by continuous muscle fiber activity. It is important to recognize that PNH may be an autoimmune phenomenon associated with antibodies targeting proteins of the voltage-gated potassium channel-complex and, in some patients, a paraneoplastic phenomenon. Symptomatic therapies include medicines that reduce neuronal excitability and in severe disease immunomodulatory treatments may be indicated.

Mercury poisoning complicated by acquired neuromyotonia syndrome: A case report.

RATIONALE: Acquired neuromyotonia syndrome is a rare form of peripheral nerve hyperexcitability syndrome. It is characterized by spontaneous and continuous muscle contractions. Acquired neuromyotonia syndrome is mainly observed in patients with autoimmune diseases or tumors, but it is a rare neurological clinical manifestation in patients with mercury poisoning. PATIENT CONCERNS: A 56-year-old woman presented with continuous and involuntary muscle twitching in her legs for 2 months; it was accompanied by a burning sensation in the lower limbs, insomnia, fatigue, and night sweats. These symptoms did not disappear during sleep. DIAGNOSES: Toxicological blood analysis via atomic fluorescence spectrometry revealed that the level of mercury was 0.07 µmol/L (normal level: <0.05 µmol/L). Her urinary mercury level measured using the cold atomic absorption method was 217.50 µmol/mol creatinine, which was considerably higher than the reference range (0-2.25 µmol/mol creatinine for people not in contact with mercury, 0-20 µmol/mol creatinine following long-term exposure). Upon further testing, a high level of mercury (10,572 mg/kg) was detected in the patient's cream. Accordingly, this patient was diagnosed with mercury poisoning. INTERVENTIONS: Treatment with 2,3-dimercapto-1-propanesulfonic acid (DMPS) was initiated. Her urinary mercury level decreased to 9.67 µmol/mol creatinine, and her neuromyotonia syndrome and hyponatremia were relieved, with urine protein completely disappearing after 3 months of treatment. OUTCOMES: After DMPS treatment, the clinical manifestations of the nervous system disappeared and electrolyte parameters returned to normal levels. LESSONS: Acquired neuromyotonia syndrome is a rare disorder caused by the hyperexcitability of peripheral nerves, resulting in spontaneous and continuous muscle contraction. Mercury poisoning should be considered in patients with neuromyotonia syndrome. Early detection of mercury poisoning can prevent unnecessary examinations and treatments.

An Unusual Case of Muscle Twitching: Its LGI1.

A 50-year-old male, presented with a two-months history of ascending paresthesias, with continuous twitchings over the body, associated with insomnia. His electromyography (EMG) revealed neuromyotonia and was diagnosed as a case of peripheral nerve hyperexcitability (PNH) syndrome due to Leucin-rich glioma-inactivated 1 (LGI1) antibody. He showed significant improvement with intravenous immunoglobulin and carbamazepine.