Mana Higashihara

RESPONSE OF ANTI-NMDA RECEPTOR ENCEPHALITIS WITHOUT TUMOR TO IMMUNOTHERAPY INCLUDING RITUXIMAB

Paraneoplastic encephalitis with antibodies against NR1/NR2 heteromers of the NMDA receptor associates frequently with ovarian teratoma and has recently been established as a distinct clinical entity.1 Most patients are young women who develop a syndrome with prodromal cold-like illness, intractable seizures, psychosis, dyskinesia, and hypoventilation.1,2 However, about 40% of patients do not have a detectable tumor,3 and the treatment of these patients remains unclear. We report a patient with anti-NR1/NR2 encephalitis without teratoma who showed a nearly complete recovery after intensive immunotherapy including rituximab. ### Case report. A 42-year-old woman had cough and headache for 3 weeks. On the day before admission, she was found to be unresponsive for several minutes, and subsequently developed generalized seizures. On admission, her temperature was 38.2°C, and she had meningeal signs. CSF revealed mild pleocytosis (10/mm3) and slightly elevated protein concentration (45 mg/dL) with normal glucose concentration and IgG index. MRI (figure, A) and EEG were unremarkable. After the seizures were controlled, minimal disorientation was observed. Acyclovir and ceftriaxone were started. Figure MRI and FDG-PET studies of the brain (A) On day 2, the FLAIR MRI was normal. (B) On day 18, the FLAIR image revealed new high-intensity areas in the right temporal cortex, insula, parts of the frontal, parietal, and occipital cortices, and hippocampus. These findings were accompanied by mild edema. High-intensity areas were also observed in the left inferior temporal cortex and hippocampus

Fasciculation potentials in amyotrophic lateral sclerosis and the diagnostic yield of the Awaji algorithm

Introduction: The role of fasciculation potentials (FPs) in the diagnosis of amyotrophic lateral sclerosis (ALS) has been underrated. The Awaji algorithm has restored the value of FPs. Our aim was to test the diagnostic yield of the Awaji algorithm, with consideration of FPs. Methods: Subjects consisted of 139 consecutive ALS patients retrospectively enrolled over 5 years. At presentation we evaluated the diagnostic categories using the revised El Escorial Criteria (R‐EEC) and the Awaji algorithm. Results: The percentage of patients classified as confirmed ALS, clinically probable (laboratory‐supported), or higher was 43% using the R‐EEC and 37% using the Awaji algorithm. Thirteen patients with upper motor neuron signs only in one body region showed a decrease in their category using the Awaji algorithm. FPs were observed in 89% of ALS patients and were frequent in proximal muscles. Conclusion: The sensitivity of the Awaji algorithm is lower than that of the R‐EEC. Muscle Nerve, 2012

Severe Hypokinesis Caused by Paraneoplastic Anti-Ma2 Encephalitis Associated with Bilateral Intratubular Germ-Cell Neoplasm of the Testes

We report a 40‐year‐old man with severe hypokinesis as paraneoplastic manifestation of a microscopic “carcinoma in situ” of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti‐Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti‐Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits.

Ultrasound-enhanced delivery of Morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice

Phosphorodiamidate morpholino oligonucleotide (PMO)-mediated control of the alternative splicing of the chloride channel 1 (CLCN1) gene is a promising treatment for myotonic dystrophy type 1 (DM1) because the abnormal splicing of this gene causes myotonia in patients with DM1. In this study, we optimised a PMO sequence to correct Clcn1 alternative splicing and successfully remedied the myotonic phenotype of a DM1 mouse model, the HSALR mouse. To enhance the efficiency of delivery of PMO into HSALR mouse muscles, Bubble liposomes, which have been used as a gene delivery tool, were applied with ultrasound exposure. Effective delivery of PMO led to increased expression of Clcn1 protein in skeletal muscle and the amelioration of myotonia. Thus, PMO-mediated control of the alternative splicing of the Clcn1 gene must be important target of antisense therapy of DM1.

Evaluation of spinal and bulbar muscular atrophy by the clustering index method

Introduction: A reliable electrophysiological marker for clinical trials is increasingly needed in spinal and bulbar muscular atrophy (SBMA). We previously developed a quantitative analysis method for surface electromyography (SEMG), the clustering index (CI) method. Our purpose was to test the utility of the CI method for evaluating lower motor neuron involvement in SBMA patients. Methods: Subjects included 29 SBMA patients and 27 healthy controls. The recording electrode was placed over the abductor digiti minimi (ADM) muscle with a proximal reference. The Z‐score, based on the CI method, was compared with compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE), with regard to sensitivity. Results: The Z‐scores of the CI method, CMAP amplitude, and MUNE were abnormal in 100%, 72%, and 93% of the patients, respectively. Interrater reliability of the CI method was sufficiently high. Conclusion: The CI method is promising as a non‐invasive electrophysiological marker in SBMA. Muscle Nerve, 2011

C8 and T1 innervation of forearm muscles.

OBJECTIVE C8-dominant innervation of ulnar-innervated and T1-dominant innervation of median-innervated intrinsic hand muscles have been suggested, although less is known regarding forearm muscles. We aimed to determine myotomal innervation of the forearm muscles based on the clinical and electromyographial findings of patients with C8 or T1 lesions. METHODS Medical Research Council scale and EMG findings were retrospectively reviewed in 16 patients with C8 lesions (2 postmedian sternotomy C8 plexopathy and 14 C8 radiculopathy) and 9 patients with T1-dominant lesions (8 true neurogenic thoracic outlet syndrome and 1 T1 radiculopathy). RESULTS Clinical and EMG findings revealed T1-dominant innervation of the flexor digitorum superficialis, flexor digitorum profundus of the index finger, abductor pollicis brevis, and flexor pollicis longus muscles, and C8-dominant innervation of the flexor carpi ulnaris, flexor digitorum profundus of the little finger, and digit extensors innervated by the posterior interosseous nerve. The first dorsal interosseous, and abductor digiti minimi muscles seem to be innervated by both C8 and T1 roots. CONCLUSIONS C8-dominant innervation of ulnar-innervated muscles and T1-dominant innervation of median-innervated muscles are also evident for forearm flexor muscles. SIGNIFICANCE Such an additional evidence for myotomal innervation will improve localization in clinical as well as electrophysiological diagnoses.

Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy

Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.

Origin of ulnar compound muscle action potential investigated in patients with ulnar neuropathy at the wrist.

The compound muscle action potential from the abductor digiti minimi muscle is bi‐lobed, and its second peak is formed by far‐field potentials (FFPs). We investigated their origin in two patients with ulnar neuropathy at the wrist that spared the hypothenar muscles. FFPs were lost or distorted, which indicated that the deep motor branch–innervated muscles, such as the interossei, mainly contributed to the FFPs, especially to their initial N1 and steep following P1 components. Muscle Nerve, 2010

Two-step technique to optimize the medial antebrachial cutaneous nerve response

OBJECTIVE Position of recording electrodes for the antidromic sensory-nerve conduction study (SCS) of the medial antebrachial cutaneous (MABC) nerve is conventionally determined according to the anatomical landmarks. However, the variation of its nerve course may interfere with accurate placement. In this study, we aimed to test how the systematic two-step examination, an orthodromic-antidromic series, affects the results. METHODS Subjects were 40 arms from 20 control subjects. For the two-step method, we first searched for the minimal threshold point over the forearm using the orthodromic technique. The recording electrode for the antidromic SCS was placed over the optimal point determined in this way. RESULTS The SNAP amplitude by our two-step method was 1.39 times (range 0.99-3.94) of that by the conventional method. Four out of 20 subjects showed greater than 50% (up to 83%) interside difference of the SNAP amplitude by the conventional methods, whereas the maximal interside difference was 38% by the two-step method. CONCLUSIONS Careful adjustment of the recording position using the two-step method would contribute to an accurate evaluation of the MABC nerve. SIGNIFICANCE To determine the recording position solely based on anatomical landmarks may cause erroneously abnormal interside difference for this nerve.

Utility of repetitive nerve stimulation test for ALS diagnosis

OBJECTIVE Decremental responses in the repetitive nerve stimulation (RNS) test in amyotrophic lateral sclerosis (ALS) patients have been reported, although their possible diagnostic role has received little investigation. We investigated their diagnostic role in differentiation between ALS and cervical spondylotic amyotrophy (CSA), an important ALS mimic especially in Japan. METHODS Patients were prospectively enrolled and the diagnosis was confirmed by follow-up. RNS was performed on the abductor pollicis brevis (APB), upper trapezius (trapezius) and deltoid muscles. RESULTS Enrolled subjects consisted of 53 ALS and 37 CSA patients. Abnormal decremental responses (>5%) were observed in 32%, 51% and 75% of ALS patients and 3%, 0% and 20% of CSA patients for the APB, trapezius and deltoid muscles, respectively. The sensitivity for 23 ALS patients with upper-limb onset was 78% for the trapezius and 100% for the deltoid muscles. CONCLUSIONS An abnormal decremental response in the trapezius muscle was 100% specific to ALS in comparison with CSA: abnormal decrement in this muscle would strongly suggest ALS. No decrement in the deltoid muscle might exclude ALS in patients having symptoms with upper-limb onset. SIGNIFICANCE RNS is useful in differentiation between ALS and CSA.