Frequency of EMG abnormalities in idiopathic inflammatory myopathies under the EULAR/ACR classification criteria.

The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for idiopathic inflammatory myopathies (IIM) have been widely used in recent times. However, no studies have focused on electromyography (EMG) findings of IIM, considering the criteria. This study aimed to elucidate the frequency of EMG abnormalities, particularly fibrillation potentials and positive sharp waves (Fib/PSW), the most objective EMG findings of IIM. Clinical and EMG records of adult patients who were clinically diagnosed with polymyositis (PM), dermatomyositis (DM), amyopathic DM (ADM), or inclusion body myositis (IBM) were retrospectively reviewed and classified according to the EULAR/ACR classification criteria. The frequency of Fib/PSW in EMG was investigated in the recruited cases. Seventy-nine patients with clinically diagnosed IIM (44 with PM, 17 with DM, 7 with ADM, and 11 with IBM) were recruited. After classification using EULAR/ACR, 75 satisfied definite or probable IIM (61 and 14, respectively), and the frequency of Fib/PSW in this group was 95%. Furthermore, the remaining 4 patients with insufficient IIM probability also showed Fib/PSW. Fib/PSW may also be seen in cases with insufficient IIM probability not satisfying the criteria. EMG may help detect muscle involvement in these cases through Fib/PSW.

Evaluation of diagnostic yield of the 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria for CIDP.

INTRODUCTION/AIMS: It is unclear whether the revised European Academy of Neurology/Peripheral Nerve Society diagnostic criteria (EAN/PNS 2021 criteria) improved the diagnostic yield for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) compared with the previous version. Therefore, this study aimed to compare the sensitivity and specificity of the EAN/PNS 2021 criteria and the European Federation of Neurological Societies/Peripheral Nerve Society 2010 diagnostic criteria (EFNS/PNS 2010 criteria), with a specific focus on the electrodiagnostic criteria. METHODS: Data of patients with clinically suspected CIDP who exhibited objective treatment response, and of those with chronic axonal neuropathies, obtained between 2009 and 2021, were extracted retrospectively from our database. Patients who underwent nerve conduction studies in at least unilateral upper and lower extremities were enrolled. We compared the sensitivity and specificity of the EAN/PNS 2021 and EFNS/PNS 2010 criteria. RESULTS: In total, 55 patients with clinically suspected CIDP and 36 patients with chronic axonal neuropathies were enrolled. When considering the "possible CIDP" category, the EAN/PNS 2021 criteria showed lower sensitivity than the EFNS/PNS 2010 criteria (78% vs. 93%, p < .05), whereas its specificity was higher (78% vs. 61%, p < .05). The lower sensitivity was caused mainly by the failure to fulfill the sensory nerve conduction criteria. The revised definition of abnormal temporal dispersion of the tibial nerve contributed markedly to the improved specificity. DISCUSSION: To improve the sensitivity of the EAN/PNS 2021 criteria, increasing the number of tested sensory nerves may be necessary.

Guillain-Barré Syndrome Mimicking Lumbar Spinal Stenosis with Segmental Weakness in L5-S1 Myotomes: Two Case Reports.

We herein report two cases of Guillain-Barré syndrome (GBS) mimicking lumbar spinal stenosis (LSS). Both cases were initially diagnosed as LSS based on prominent segmental weakness in the L5 and S1 myotomes and coexisting LSS on magnetic resonance imaging. However, neurological and electrophysiological examinations revealed abnormalities that extended to the upper extremities, although slight, prompting us to suspect GBS. Subsequently, serum antiganglioside antibodies and remarkable responsiveness to intravenous immunoglobulin therapy confirmed GBS. We suspect that the focal blood-nerve barrier disruption due to preexisting LSS might have contributed to the segmental weakness in this atypical GBS case.

[A case of acute bilateral blindness presumably caused by reversible cerebral vasoconstriction syndrome after traumatic brain injury].

A 62-year-old man was admitted to our hospital for acute bilateral blindness two days after a head injury. Hemorrhagic cerebellar infarction was found on the initial MRI, and peripheral arteries were poorly visualized on MRA. On the follow-up MRA nine days later, peripheral arteries were clearly depicted. These imaging findings suggested reversible cerebral vasoconstriction syndrome (RCVS). We started steroid pulse therapy for suspected optic neuritis with no clear response. The initial fundoscopic examination revealed no abnormalities in the optic disc, but optic nerve atrophy developed one month later. Based on the course of events, we diagnosed the patient with posterior ischemic optic neuropathy triggered by RCVS.

Different Tendencies in Muscle Ultrasound Characteristic in Amyotrophic Lateral Sclerosis and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

INTRODUCTION: The difference in muscle ultrasound (MUS) characteristics in primary axonal degeneration and demyelination has not been well established. The authors aimed to investigate the subject based on the correlation between MUS findings (echo intensity and muscle thickness) and compound muscle action potential (CMAP) amplitude in amyotrophic lateral sclerosis (ALS) and chronic inflammatory demyelinating polyradiculoneuropathy. METHODS: Fifteen patients with ALS and 16 patients with chronic inflammatory demyelinating polyradiculoneuropathy were examined. For each patient, echo intensity and muscle thickness of the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were investigated. Compound muscle action potential amplitudes were measured by median and ulnar nerve conduction studies. RESULTS: In total, 45 muscles were evaluated in each group. The ALS group showed a linear correlation between the MUS finding and CMAP amplitude (rs = -0.70 and 0.59 for echo intensity and muscle thickness, respectively), whereas the chronic inflammatory demyelinating polyradiculoneuropathy group showed a weaker correlation than the ALS group (rs = -0.32 for echo intensity and rs = 0.34 for muscle thickness). CONCLUSIONS: The relationship between MUS abnormalities and CMAP amplitude showed different tendencies in ALS and chronic inflammatory demyelinating polyradiculoneuropathy. The results suggested that MUS abnormalities substantially reflect the muscle function in primary axonal degeneration, whereas a discrepancy between MUS findings and muscle function can be frequently seen in demyelination; specifically, MUS findings tend to be normal even though CMAP showed a reduction. These tendencies originating from underlying pathophysiology should be considered when MUS findings are used as biomarkers of disease severity.

Weak gluteus maximus and weak iliopsoas with normal gluteus maximus: Two complementary new signs to diagnose lower limb functional weakness.

BACKGROUND AND PURPOSE: The diagnosis of functional neurological disorder should be actively made based on the neurological signs. We described two new complementary signs to diagnose functional weakness of the lower limb, "weak gluteus maximus (weak GM)" and "weak Iliopsoas with normal gluteus maximus (weak iliopsoas with normal GM)," and tested their validity. METHODS: The tests comprised Medical Research Council (MRC) examinations of the iliopsoas and GM in the supine position. We retrospectively enrolled patients with functional weakness (FW) or structural weakness (SW) who presented with weakness of either iliopsoas or GM, or both. Weak GM means that the MRC score of GM is 4 or less. Its complementary sign, weak ilopsoas with normal GM, means that the MRC score of ilopsoas is 4 or less, whereas that of GM is 5. RESULTS: Thirty-one patients with FW and 72 patients with SW were enrolled. The weak GM sign was positive in all 31 patients with FW and in 11 patients with SW, that is, 100% sensitivity and 85% specificity. Therefore, the complementary sign, weak iliopsoas with normal GM, was 100% specific for SW. DISCUSSION: Although 100% should be discounted considering limitations of this study, these signs will likely be helpful in differentiating between FW and SW in the general neurology setting. Downward pressing of the lower limb to the bed in the supine position is interpreted by the patient as an active movement exerted with an effort and might be preferentially impaired in FW.

Noncanonical splice-site variant in peripheral myelin protein 22 gene (PMP22) in a patient with hereditary neuropathy with liability to pressure palsies.

AIM: Hereditary neuropathy with liability to pressure palsies (HNPP) is a peripheral neuropathy with autosomal dominant inheritance. Diagnosis can be made from the characteristic abnormalities determined by nerve conduction studies (NCS), including subclinical deficits at physiological compression sites. Heterozygous deletion of the chromosome 17p11.2-p12 region including the peripheral myelin protein 22 gene (PMP22) is the cause in the majority of cases. However, the loss of function of PMP22 due to frameshift-causing insertion/deletion, missense, nonsense, or splice-site disrupting variants cause HNPP in some patients. We report a case of a patient diagnosed with HNPP on the basis of clinical features and the results of NCS. No deletions of PMP22 were detected by fluorescence in situ hybridization. METHODS: We performed direct nucleotide sequence analysis and identified a heterozygous variant, c.78 + 3G > T, in PMP22. Since this variant is located outside the canonical splice site at the exon 2-intron 2 junction, we investigated whether the variant causes aberrant splicing and leads to the skipping of exon 2 of PMP22 by in vitro minigene splicing assay. RESULTS: We demonstrated that the c.78 + 3G > T variant causes the skipping of exon 2 and leads to loss of function of the mutant allele. CONCLUSION: Searching for sequence variants located outside the canonical splice sites should also be considered even when deletion of PMP22 is not found in a patient with a clinical diagnosis suggesting HNPP.

Utility of nerve ultrasound in the management of primary neurolymphomatosis: Case report and review of the literature.

Introduction: Primary neurolymphomatosis (NL) is a critical differential diagnosis of asymmetric multiple mononeuropathy and radiculoplexopathy. Its diagnosis is often challenging due to the lack of typical clinical signs of systemic lymphoma. We report a case of primary NL where nerve ultrasound (NUS) played an important role in the diagnosis and follow-up of the disease. Case presentation: A 52-year-old man developed asymmetric painful multiple mononeuropathy in the right upper limb with cranial nerve involvement. After being referred to our department, the patient underwent NUS, which revealed marked enlargement and increased vascularity in the right upper limb nerves, brachial plexus, and cervical nerve roots. Furthermore, an epineural hypoechoic mass, a characteristic finding of NL, was seen in the right median nerve. These NUS findings prompted us to perform 18F-fluorodeoxyglucose positron emission tomography/computed tomography and a subsequent biopsy on the right axillary lymph node, confirming NL. Notably, the NUS abnormalities dramatically subsided, demonstrating the effectiveness of chemotherapy. Discussion: The diagnostic utility of NUS for NL has been documented by many recent reports. Additionally, NUS can work as a quick follow-up tool for NL, as seen in our case.

Immunotherapy for ocular myasthenia gravis: an observational study in Japan.

Background: Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. Objectives: We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. Design: We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Methods: Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. Results: In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower (p = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Conclusion: Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Plain language summary: Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG.

Tibial nerve SEPs in diagnosing lumbar spinal stenosis: The utility of segmental evaluation using P15 and N21.

Objective: To establish the utility of the additional evaluation of the P15 potential generated at the greater sciatic foramen in the tibial nerve somatosensory evoked potentials (SEPs) in diagnosing lumbar spinal stenosis (LSS). Methods: We retrospectively reviewed tibial nerve SEP findings in patients having MRI-confirmed LSS at the cauda equina or conus/epiconus region. P15 and N21 potentials were recorded and the following findings were defined as localizing abnormalities: 1) normal P15 latency either with prolonged P15-N21 interval or with absent N21; 2) decreased ratio of the N21 amplitude to P15 amplitude. As non-localizing abnormalities, N21 and P38 latencies were also evaluated. Tibial nerve F-wave findings were also investigated. Results: According to the entry criteria, 18 patients were included, 15 with cauda equina lesions and 3 with conus/epiconus lesions. Localizing abnormalities in SEPs were found in 67% of patients, achieving significantly higher sensitivity than delayed P38 latency (28%), and higher sensitivity than N21 abnormalities (39%), though this was not significant. Localizing abnormalities were observed even in 6 out of 11 patients lacking both sensory symptoms and signs. Tibial nerve F-wave was abnormal in 36% of 14 patients with F-wave examinations, whereas the localizing abnormalities in SEPs were found in 64% of the same patient population. P15 amplitude was depressed in 4 patients (22%), which may indicate the involvement of the dorsal root ganglion in LSS, although its latency was normal even for these patients. Conclusions: Tibial nerve SEPs with the recording of P15 and N21 potentials achieved sufficiently high sensitivity in diagnosing LSS. They have the advantage over F-wave in that they can localize the lesion at the cauda equina or conus/epiconus level. Significance: Tibial nerve SEPs are promising in evaluating LSS, especially in documenting sensory tract involvement in cases lacking sensory symptoms/signs.

Idiopathic Inflammatory Myopathy with Delayed Finger Opening Resembling Grip Myotonia.

Grip myotonia can be a clue for the diagnosis of myotonic disorders. However, several clinical conditions cause delayed finger opening mimicking grip myotonia. We herein report a 44-year-old man with idiopathic inflammatory myopathy who presented with delayed finger opening resembling grip myotonia. The delayed finger opening differed from grip myotonia given the absence of the warm-up phenomenon and percussion myotonia, relative sparing of the thumb extension, and pronounced weakness of the extensor digitorum. Focusing on the extension of the thumb and other fingers may aid in the differentiation between delayed finger opening and true grip myotonia.

Far-field potential of the compound muscle action potential as a reliable marker in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS. METHODS: Patients with ALS and age-matched healthy controls were enrolled. We used a proximal reference (pref) in addition to the conventional distal reference (dref). Routine CMAP was recorded from the belly-dref lead and FFP-CMAP from the dref-pref lead for the ulnar and tibial nerves. Multiple point stimulation motor unit number estimation (MUNE) was also examined in the ulnar nerve. Inter-rater reproducibility was evaluated by two examiners, and some patients were followed up every 3 mo for 1 y. RESULTS: We tested 17 patients with ALS and 10 controls. The amplitudes of routine CMAP and FFP-CMAP in the ulnar and tibial nerves, and hypothenar MUNE value in the ulnar nerve were significantly decreased in ALS compared to controls. Ulnar FFP-CMAP achieved the highest inter-rater intraclass correlation coefficient (ICC) value (0.942) when compared with routine CMAP (0.880) and MUNE (0.839). The tibial FFP-CMAP had a higher ICC value (0.986) than the routine CMAP (0.697). In this way, the FFP-CMAP showed high inter-rater reproducibility because its shape was not much influenced by the electrode position. During 1-y follow-up, decline of CMAP, FFP, and MUNE showed significant correlations with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). DISCUSSION: The FFP-CMAP shows promise as a reliable marker for ALS.

[Borderline regions between neurology and psychiatry, focusing particularly on the functional neurological disorders].

Neurology in Japan did not develop from the separation of neuropsychiatry into neurology and psychiatry, which casts a shadow on the present situation of Japanese neurology. Functional neurological disorder (FND; hysteria) is a typical link between neurology and psychiatry. FND is a common disorder, which has been described from the ancient times and has also been the headstream of neurology. FND is not diagnosed by exclusion or by psychiatric causes, but should be actively diagnosed based on the neurological signs themselves (= positive signs of FND) as early as possible, with minimal ancillary tests. This opinion has been supported by the newest Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Many positive signs have been described. Assessment by a neurologist also becomes a treatment.

Recent advances in neuroanatomy: the myotome update.

The myotome of a muscle is the basis for diagnosing spinal and peripheral nerve disorders. Despite its critical importance in clinical neurology, myotome charts presented in many textbooks, surprisingly, show non-negligible discordances with each other. Many authors do not even clearly state the bases of their charts. Studies that have presented with raw data regarding myotome identification are rather rare. A classic study in the 19th century that pursued the nerve course in cadavers still has a substantial influence on existing charts, despite its definite limitations. Other scarce studies in humans include identification by root stimulation during surgery, clinical observations in root avulsion or spinal cord injury and clinical and electromyographical investigations in patients with single radiculopathies or certain plexopathies. A few recent studies have proposed new theories regarding the myotomes of some muscles. T1 innervation of the median intrinsic hand muscles is a typical example. We have added a number of new findings, such as T1 innervation of the forearm flexor muscles innervated by the median nerve except the pronator teres and flexor carpi radialis, C5 innervation of the brachioradialis, and two C6 indicator muscles, pronator teres and extensor carpi radialis brevis. Increased accuracy of the myotome charts will improve the localisation in neurology.

Utility of the tibial nerve somatosensory evoked potentials in differentiating between neuromyelitis optica spectrum disorders and multiple sclerosis.

BACKGROUND: Somatosensory evoked potentials (SEPs) are widely used for the diagnosis and evaluation of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). However, whether the parameters of tibial nerve SEPs can help to distinguish NMOSD from MS remains unclear. Thus, the aim of this study was to investigate the utility of tibial nerve SEP parameters in differentiating patients with NMOSD and MS. METHODS: The clinical data of patients with NMOSD or MS treated in our institution between 2005 and 2021 were retrospectively extracted from our electronic database. Additional inclusion criteria were presentation with sensory symptoms in the lower extremities with corresponding lesions in the magnetic resonance images as well as available data on anti-aquaporin-4 antibodies and tibial nerve SEPs. The Z-scores of the N21-P38 interval (central sensory conduction time), P38 latency, and P38 amplitude were compared between the patients with NMOSD and MS. The relationship of disease severity with the parameters of the tibial nerve SEPs was also evaluated. RESULTS: Twenty patients with NMOSD and 13 patients with MS were enrolled. The Z-scores of the N21-P38 interval and P38 latency were significantly higher in the MS group than in the NMOSD group (p < 0.05 and p < 0.01, respectively), whereas there was no difference in the Z-scores of the P38 amplitude between the two groups. In the MS group, only the N21-P38 interval and P38 latency were significantly correlated with disease severity (p < 0.05 and p < 0.01, respectively). In contrast, none of the tibial nerve SEP parameters were significantly correlated with disease severity in the NMOSD group. CONCLUSION: Evaluation of the N21-P38 interval and P38 latency in tibial nerve SEPs potentially helps in differentiating between NMOSD and MS.

[Finger drop variant of Guillain-Barré syndrome: a case report].

We report the case of a 31-year-old man with a finger drop variant of Guillain-Barré syndrome (GBS). The patient visited a neurological clinic with complaints of difficulty in extending the fingers, which occurred seven days after he had fever and diarrhea. The physician who first saw the patient suspected posterior interosseous nerve palsy and referred him to our hospital. Neurological examination 35 days after the onset revealed distal weakness of the upper extremities, particularly in the bilateral extensor digitorum (Medical Research Council [MRC] scale 1/1 [right/left]). The left triceps surae muscle was also weak (MRC scale 5/4). Bilateral Achilles tendon reflexes were absent, but other neurological findings were normal. Cerebrospinal fluid examination showed albuminocytologic dissociation. Serum immunoglobulin G antibodies against GM1 were positive. Nerve conduction studies revealed reduced amplitude of compound muscle action potentials (CMAPs) without evidence of demyelination in the median, ulnar, radial, and tibial nerves. CMAP amplitude was most severely reduced in the radial nerve among the upper extremity nerves. We diagnosed the patient with acute motor axonal neuropathy. His symptoms gradually improved after treatment with intravenous immunoglobulin. When encountering acute finger drop, neurologists should consider the finger drop variant of GBS as a differential diagnosis.

Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: The effectiveness of currently approved drugs for amyotrophic lateral sclerosis (ALS) is restricted; there is a need to develop further treatments. Initial studies have shown ultrahigh-dose methylcobalamin to be a promising agent. Objective: To validate the efficacy and safety of ultrahigh-dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design, Setting, and Participants: This was a multicenter, placebo-controlled, double-blind, randomized phase 3 clinical trial with a 12-week observation and 16-week randomized period, conducted from October 17, 2017, to September 30, 2019. Patients were recruited from 25 neurology centers in Japan; those with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score, a percent forced vital capacity greater than 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulatory. The target participant number was 64 in both the methylcobalamin and placebo groups. Patients were randomly assigned through an electronic web-response system to methylcobalamin or placebo. Interventions: Intramuscular injection of methylcobalamin (50-mg dose) or placebo twice weekly for 16 weeks. Main Outcomes and Measures: The primary end point was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: A total of 130 patients (mean [SD] age, 61.0 [11.7] years; 74 men [56.9%]) were randomly assigned to methylcobalamin or placebo (65 each). A total of 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Of these, 124 patients proceeded to the open-label extended period. The least square means difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (-2.66 vs -4.63; 95% CI, 0.44-3.50; P = .01). The incidence of adverse events was similar between the 2 groups. Conclusions and Relevance: Results of this randomized clinical trial showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in patients with early-stage ALS and with moderate progression rate and was safe to use during the 16-week treatment period. Trial Registration: ClinicalTrials.gov Identifier: NCT03548311.