BACKGROUND: Isaacs\' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings include cramps, fasciculations, and myokymia; however, there are few reports of dental treatment for trismus.
METHODS: A patient with trismus due to Isaacs\' syndrome experienced swelling and pain in the gingiva surrounding his right lower first molar. He was diagnosed with chronic apical periodontitis by a dentist near his home. However, the patient was informed that dental treatment and medication could not be administered because of the presence of Isaacs\' syndrome, and he visited the Geriatric Dentistry and Perioperative Oral Care Center at Kyushu University Hospital 2 weeks later. The patient\'s painless mouth-opening distance (between incisors) was 20 mm at that time, and medication, including amoxicillin capsules and acetaminophen, was administered because the dental extraction forceps or endodontic instruments were difficult to insert into the oral cavity for treatment. Two months after his initial visit, the patient visited us complaining of pain in the same area. However, he had recently undergone plasmapheresis treatment in neurology to alleviate limited mouth opening and systemic myalgia, resulting in a pain-free mouth-opening distance of approximately 35 mm. During this temporary period in which he had no restriction in mouth opening, we performed tooth extraction and bridge restoration on the mandibular right first molar and created an oral appliance for sleep bruxism.
CONCLUSIONS: Plasmapheresis therapy transiently reduced trismus, rendering dental interventions feasible, albeit temporarily. This case report underscores the importance of close collaboration between neurologists and dentists who encounter similar cases while furnishing valuable insights to inform dental treatment planning.

UNASSIGNED: Peripheric nerve hyperexcitability (PNH) syndromes are a rare, heterogenous group of diseases characterized by continuous muscle overactivity due to spontaneous discharges of the lower motor neurons.
UNASSIGNED: Here we report four patients presented with painful cramps, generalized muscle twitches and lower extremity weakness. All patients had evidence of neuropathy and neuromyotonic discharges on electrodiagnostic studies. Screening for a broad panel of anti-neuronal antibodies proved uncharacterized neuropil antibodies in one patient. Despite extensive serologic and genetic investigations, no definitive etiology was found in our cohort. One out of three patients responded well to immunotherapy. No other diseases including malignancy appeared for 1.5-3 years follow-up duration.
UNASSIGNED: Our case series indicate a putatively high prevalence of neuropathy in PNH and emphasize anti-neuronal antibody positivity and early diagnosis as potential favorable prognostic factors.

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.

OBJECTIVE: Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis.
METHODS: Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared.
RESULTS: In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T2WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P<0.05).
CONCLUSIONS: Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.
目的: 抗富亮氨酸胶质瘤失活蛋白1(leucine-rich glioma-inactivated protein 1，LGI1)抗体、抗接触蛋白相关蛋白2(contactin-associated protein-like 2，CASPR2)抗体引起的自身免疫性脑炎较为罕见，临床异质性大，极易漏诊、误诊。本研究旨在总结抗LGI1抗体及抗CASPR2抗体脑炎患者的临床特征。方法: 收集2018年1月至2021年1月中南大学湘雅医院神经内科收治的抗LGI1抗体、抗CASPR2抗体脑炎患者共28例，所有患者进行自身免疫性脑炎相关抗体谱及副肿瘤抗原谱抗体筛查。回顾性分析28例患者的临床表现、辅助检查资料、治疗及随访情况，采用改良Rankin量表评估患者治疗前后的生活能力，并对这2种自身免疫性脑炎的临床特征进行比较和分析。结果: 28例中抗LGI1抗体脑炎17例，发病年龄28~83(53.18±19.08)岁，男女患者之比为9꞉8。临床表现为认知功能障碍的患者有10例，癫痫发作7例，面臂肌张力障碍发作4例，精神行为异常1例。实验室检查发现低钠血症7例；脑脊液检查异常4例，表现为白细胞数或蛋白质含量轻度上升各2例；脑电图异常13例，主要表现为慢波增多(8/13)及痫性放电(5/13)；颅脑磁共振成像(magnetic resonance imaging，MRI)异常13例，主要表现为颞叶、海马及基底节区T2加权成像(T2-weighted imaging，T2WI)及水抑制反转恢复序列(fluid attenuated inversion recovery，FLAIR)呈高信号。抗CASPR2抗体脑炎患者11例，发病年龄17~68(47.18±16.20)岁，男女患者之比为5꞉6。7例为边缘性脑炎，1例为莫旺综合征，3例为获得性神经性肌强直；临床表现为癫痫发作者4例，精神行为异常、认知障碍和意识障碍各1例；脑脊液异常3例，主要表现为白细胞数及蛋白质含量轻度升高；脑电图异常5例，主要表现为慢波增多(3/5)及痫性放电(2/5)；颅脑MRI异常2例，主要表现为颞叶、海马T2WI及FLAIR高信号。16例抗LGI1抗体脑炎及8例抗CASPR2抗体脑炎患者使用糖皮质激素、免疫球蛋白及血浆置换等一线免疫治疗，均反应良好，其中1例抗LGI1抗体脑炎及3例抗CASPR2抗体脑炎患者同时口服吗替麦考酚酯维持治疗；采用免疫治疗的患者除2例失访外，随访期内(6~36个月)均未见明显复发。2种抗体脑炎在认知障碍、低钠血症、颅脑MRI异常上差异均有统计学意义(均P<0.05)。结论: 抗LGI1抗体及抗CASPR2抗体脑炎均可表现为边缘性脑炎，抗LGI1抗体脑炎以认知障碍为主要表现，面臂肌张力障碍发作及低钠血症为特征性表现，易出现颅脑MRI异常；抗CASPR2抗体脑炎以癫痫发作为最常见临床表现，可累及周围神经系统而出现神经性肌强直、莫旺综合征且易合并肿瘤。2种抗体脑炎均对免疫治疗敏感，预后良好。.

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.

Recessive loss-of-function variations in HINT1 cause a peculiar subtype of Charcot-Marie-Tooth disease: neuromyotonia and axonal neuropathy (NMAN; OMIM[#137200]). With 25 causal variants identified worldwide, HINT1 mutations are among the most common causes of recessive neuropathy. The majority of patients are compound heterozygous or homozygous for a Slavic founder variant (c.110G>C, p.Arg37Pro) that has spread throughout Eurasia and America.
In a cohort of 46 genetically unresolved Lithuanian patients with suspected inherited neuropathy, we identified eight families with HINT1 biallelic variations. Most patients displayed sensorimotor or motor-predominant axonal polyneuropathy and were homozygous for the p.Arg37Pro variant. However, in three families we identified a novel variant (c.299A>G, p.Glu100Gly). The same variant was also found in an American patient with distal hereditary motor neuropathy in compound heterozygous state (p.Arg37Pro/p.Glu100Gly). Haplotype analysis demonstrated a shared chromosomal region of 1.9 Mb between all p.Glu100Gly carriers, suggesting a founder effect. Functional characterization showed that the p.Glu100Gly variant renders a catalytically active enzyme, yet highly unstable in patient cells, thus supporting a loss-of-function mechanism.
Our findings broaden NMAN\'s genetic epidemiology and have implications for the molecular diagnostics of inherited neuropathies in the Baltic region and beyond. Moreover, we provide mechanistic insights allowing patient stratification for future treatment strategies.

Inherited peripheral neuropathy (IPN) is a heterogeneous group of disorders due to pathogenic variation in more than 100 genes. In 2012, the first cases of IPN associated with HINT1 pathogenic variations were described in 33 families sharing the same phenotype characterized by an axonal neuropathy with neuromyotonia and autosomal recessive inheritance (NMAN: OMIM #137200). Histidine Triad Nucleotide Binding Protein 1 regulates transcription, cell-cycle control, and is possibly involved in neuropsychiatric pathophysiology. Herein, we report seven French patients with NMAN identified by Next Generation Sequencing. We conducted a literature review and compared phenotypic and genotypic features with our cohort. We identified a new HINT1 pathogenic variation involved in NMAN: c.310G>C p.(Gly104Arg). This cohort is comparable with literature data regarding age of onset (7,4yo), neuronal involvement (sensorimotor 3/7 and motor pure 4/7), and skeletal abnormalities (scoliosis 3/7, feet anomalies 6/7). We expand the phenotypic spectrum of HINT1-related neuropathy by describing neurodevelopmental or psychiatric features in six out of seven individuals such as generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), mood disorder and attention deficit hyperactivity disorder (ADHD). However, only 3/128 previously described patients had neuropsychiatric symptomatology or neurodevelopmental disorder. These features could be part of HINT1-related disease, and we should further study the clinical phenotype of the patients.

暂无摘要。

Autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) is a rare hereditary neuropathy within the Charcot-Marie-Tooth disease (CMT) spectrum, linked to mutations in the histidine triad nucleotide-binding protein 1 (HINT1) gene. HINT1-related neuropathy is particularly common in selected populations from Central and Eastern Europe but rare in Western European cohorts. It has not been investigated to date in the Greek population. We presently investigated the frequency of HINT1-neuropathy in a selected cohort of 42 Greek index patients with autosomal recessive or sporadic axonal hereditary neuropathy according to standard molecular genetics procedures. We identified 4 patients with biallelic mutations in HINT1, comprising 9.5% of all cases and 44.4% of cases also displaying neuromyotonia. The c.110G> C (p.Arg37Pro) HINT1 mutation was present in all cases (2 homozygous) and the c.250T> C (p.Cys84Arg) in 2 cases (compound heterozygous). HINT1-related neuropathy patients were characterized by early onset and neuromyotonia. Two patients had noteworthy clinical features, one case developing myoclonic epilepsy and the other displaying \"adducted thumbs.\" We conclude that HINT1-related neuropathy is common in selected Greek patients with hereditary neuropathy within the CMT spectrum, in accordance with some, but not all, European populations.

UNASSIGNED: Hemifacial spasm is diagnosed on a clinical base, with certain atypical features alerting the physician for mimics.
UNASSIGNED: Hemifacial neuromyotonia/myokymia characterized by tonic hemifacial contraction followed by multifocal undulating hemifacial twitches.
UNASSIGNED: These features are a red flag for (post-irradiation) facial neuromyotonia/myokymia which generally responds well to low dose carbamazepine.