OBJECTIVE: Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs.
METHODS: This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years.
RESULTS: A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years.
CONCLUSIONS: Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.

BACKGROUND: KCNJ10 and CAPN1 variants cause \"spinocerebellar\" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear.
OBJECTIVE: To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia.
METHODS: Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs.
METHODS: Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples.
RESULTS: Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs.
CONCLUSIONS: The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.

Peripheral nerve hyperexcitability is an uncommon but treatable condition in neurology. Voltage-gated potassium channelopathies, especially contactin-associated protein-like 2 (CASPR2) antibody, are commonly implicated. We present the case of a 16-year-old boy with tremulousness of both feet and twitching of muscles all over the body for three months. Examination revealed irregular, arrhythmic, small-amplitude twitching movements of the toes along with fasciculations in both thighs. Nerve conduction studies were within normal limits. F-wave studies showed a prolonged polyphasic large-amplitude discharge following the compound muscle action potential and obscuring the F waves. Electromyography showed extensive myokymic discharges. The serum autoimmune antibody profile showed strong positivity for CASPR2. He started lacosamide as a symptomatic treatment. In view of the good symptomatic response, further immunomodulation was deferred and he remains on follow-up. We present this case to highlight the role of motor afterdischarges as a diagnostic clue to peripheral nerve hyperexcitability and to review the literature on this interesting finding.

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.

Contactin-associated protein-like 2 autoimmunity is an uncommon disorder resulting in peripheral nerve hyperexcitability or encephalitis. In a fifth of cases, onset may be provoked by thymoma, but other associations are largely unknown. We report a patient with anti-contactin-associated protein-like 2-related peripheral nerve hyperexcitability arising in the setting of Charcot-Marie-Tooth type 4F and discuss potential mechanisms underlying the association.

Isaac syndrome (IS) is a peripheral nerve hyperexcitability state associated with voltage-gated potassium channel (VGKC) complex antibodies. Major manifestations are muscle twitching, stiffness, hypertrophy, and dysautonomic features such as hyperhidrosis [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Neuropathic pain is a rare manifestation. We describe a case of IS characterized by muscle twitching and intractable neuropathic pain. Diagnostic workup included elevated VGKC complex antibodies and EMG/NC that showed neuromyotonic discharges. Neuropathic pain was initially difficult to relieve even after using multiple medications, including opiates, benzodiazepines, anticonvulsants, and intravenous immunoglobulin (IVIg). Moderate pain control was eventually achieved with long-term use of carbamazepine and subcutaneous immunoglobulin (SCIg). Common manifestations of IS are muscle twitching, stiffness hypertrophy, and dysautonomia [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Sensory manifestations such as neuropathic pain are rare, but, as illustrated by our patient, can be the most distressing symptom. In our patient, not only was neuropathic pain disabling but it also showed the least response to IVIg. The use of 200 mg of long-acting carbamazepine twice daily with weekly SCIg demonstrated the best response. This case highlights an uncommon but potentially resistant symptom of IS.

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.

UNASSIGNED: Peripheral nerve hyperexcitability (PNH) and neuromyotonia have been mainly attributed to antibodies against voltage-gated potassium channels (VGKC). Concurrent autoimmune disorders, malignancies, and heavy metal toxicity have also been implicated. There is scarce mention about infection as a triggering factor for PNH. There are no reports of methicillin-resistant Staphylococcus aureus (MRSA) infection being a possible precipitating factor for development of PNH.
UNASSIGNED: Case series and literature review.
UNASSIGNED: Four subjects were diagnosed to have features of PNH based on clinical and electrophysiological assessment. All the subjects had concurrent evidence of cutaneous abscesses requiring surgical intervention and antibiotic therapy. The cultures in all of them revealed growth of Staphylococcus aureus with three of them being MRSA isolates. Two subjects tested positive for anti-VGKC antibodies. There was remarkable resolution in neuromyotonia after antibiotics in three subjects. One subject succumbed to fulminant MRSA septicemia.
UNASSIGNED: There appears to be a definitive link between staphylococcal infection (MRSA in particular) and development of PNH. The temporal evolution of PNH associated with the infection and resolution following treatment of the infection does support a causal association. The enterotoxins produced by staphylococci act as superantigens and could trigger an inflammatory cascade along with development of cross reacting antibodies against VGKC in peripheral nerves. Future studies with animal models could provide more directions in this regard.

Introduction: This study aimed to analyze the clinical features of myasthenia gravis (MG) in combination with the afterdischarges and compare the characteristics of afterdischarges in MG with different serum antibodies. Methods: Ninety-two patients with MG were analyzed retrospectively. The afterdischarges were investigated using motor nerve conduction examination, F-wave examination, and repetitive nerve stimulation (RNS). Results: Afterdischarges were observed after the M wave in 14 of 92 patients. Three of these 14 patients tested positive for the muscle-specific tyrosine kinase antibody (MuSK-Ab), and 11 patients tested positive for the acetylcholine receptor antibody (AchR-Ab). The characteristics of the afterdischarges on RNS differed distinctly between the two antibody groups. The afterdischarges occurred on the first stimulation, but decreased on the second and subsequent stimulations in patients with MuSK-MG, while the afterdischarges continued to occur on each stimulation in patients with AchR-MG. Discussion: The characteristics of the afterdischarges on RNS enabled easy identification of their synaptic or neurogenic nature.

Limited literature is available on stimulus induced after discharges (SIAD) in patients with peripheral nerve hyperexcitability (PNH). The aim of the study was to examine the diagnostic utility of SIAD in the diagnosis and monitoring of primary PNH disorders. In this retrospective study, we studied 26 patients who were admitted with a diagnosis of primary PNH to the department of Neurology from January 2013 to April 2019. Their clinical profile, immunological characteristics were extracted from the database and nerve conduction studies were relooked for the presence of SIAD. 76% of patients in the primary PNH cohort had SIAD with 90% of them being voltage-gated potassium channel complex antibody positive; predominantly against contactin-associated protein-2 antigen and rest being paraneoplastic. There was also resolution of SIAD following treatment indicating reversible hyperexcitability. SIAD is a sensitive marker for Primary PNH syndrome with monitoring and diagnostic implications.