Nozomu Matsuda

Mutations in MME cause an autosomal-recessive Charcot–Marie–Tooth disease type 2

The objective of this study was to identify new causes of Charcot–Marie–Tooth (CMT) disease in patients with autosomal‐recessive (AR) CMT.

Micturitional disturbance due to bilateral medial frontal lobe lesions in a patient with multiple sclerosis

A 41-year-old man with multiple sclerosis (MS) complained of nocturnal enuresis at the third exacerbation. Neurological examination revealed echopraxia, forced grasp reflexes and palmo-mental reflexes. The urodynamic studies showed neither spinal cord nor peripheral nerve involvements. His brain magnetic resonance images (MRIs) revealed new lesions at the bilateral medial frontal lobes. The intravenous methylprednisolone therapy improved nocturnal enuresis and made brain MRI lesions smaller and gone. In addition to frequently observed spinal cord lesions, we should consider some medial frontal lesions to be responsible for micturitional disturbance in patients with MS.

Three cases of interstitial pneumonia with anti-signal recognition particle antibody

Anti-signal recognition particle antibody (SRP-Ab) is a myositisspecific antibody (MSA) that is found in serum of patients with myositis characterized by a necrotizing myopathy. Because patients with SRP-Abs have few extra-muscular manifestations,1 the clinical characteristics of interstitial pneumonia (IP) with SRP-Ab have not been clarified. Here, we present three cases of IP with SRP-Ab. Case 1: A 51-year-old man with a one-year history of cough and sputum was referred to our hospital for gradual progression of his symptoms. On admission, he did not have muscle pain or proximal muscle weakness. CK was markedly elevated (1160 U/L), and aldolase (16.2 U/L), KL-6 (1529 U/mL) and SP-D (312.4 ng/mL) were also elevated. Auto-immune antibodies analyzed were negative. Pulmonary function tests revealed restrictive respiratory dysfunction. His

Role of Skeletal Muscle MRI inPeripheral Nerve Disorders

In diagnosing peripheral nerve disorders, the involved nerves can usually be determined based on clinical history and neurological findings with the aid of electrophysiological examinations. Despite the principle, we often encounter diagnostic challenges. In this chapter, we describe the clinical utility of magnetic resonance imaging (MRI) for the evaluation of peripheral nerve disorders. MRI can visualize pathological changes in skeletal muscles secondary to lesions of the peripheral nerve, plexus or nerve root. The lesion sites may be inferred based on the distribution of the involved muscles. After the first report in 1987 (Shabas et al., 1987), MRI has increasingly been used to evaluate denervated muscles (West et al., 1994; Fleckenstein et al., 1993; Uetani et al., 1993). In particular, studies of entrapment or compressive neuropathy have greatly contributed to the understanding of clinical-radiological correlations in peripheral nerve damage. Animal experiments have also been conducted, in which muscle MRI was examined after peripheral nerve transection. MRI has several distinct advantages over needle electromyography (EMG), including noninvasiveness, accessibility to deep muscles and interexaminer reliability (Koltzenburg and Bendszus, 2004; Bendszus et al., 2003; McDonald et al., 2000). MRI is particularly useful as needle EMG is difficult to perform on children or patients on anticoagulation. Excellent spatial resolution allows MRI to detect atrophy of the small muscles, moreover, different MRI pulse sequences show sensitivity to different stages of denervation, thus, MRI can provide valuable information about the duration of muscle denervation (Kamath et al., 2008). MRI has a potential to visualize mass lesions causing nerve damage, such as tumours, which is useful for the clinical judgment of surgical resectability (Grant et al., 2002). An abnormal MR signal in muscles is not specific to denervation and may also be seen in any condition that causes muscle edema, including severe muscle strains, blunt trauma and acute myositis. Thus, MRI findings need to be interpreted in combination with other clinical information. Previous muscle MRI studies of peripheral nerve disorders have mostly focused on entrapment or compression neuropathy (Andreisek et al., 2006; Petchprapa et al., 2010; Donovan et al., 2010). However, given its capability in visualizing pathological changes and mapping the distributions of the involved muscles, the use of MRI can be extended to a variety of peripheral nerve disorders. We will give a theoretical background of muscle MRI and describe its clinical applications in peripheral nerve disorders with some representative cases. We will also mention non-muscular features of MRI, e.g. nerve signal

Thoracoabdominal muscle involvement in anti-PL-7 myopathy revealed by whole-body magnetic resonance imaging

A 33-year-old woman developed progressive weakness in the proximal limbs with myalgia and morning stiffness. Physical examination revealed low-grade fever, heliotrope eyelids and mechanics hand. On neurological examination, she showed Medical Research Council grade 4 weakness in the shoulder girdle, proximal limb muscles, and grade 4 weakness in the abdominis muscle according to Danielss scale. Laboratory tests revealed elevated serum creatine kinase (6,824 IU/l) and positive anti-PL-7 antibody. A needle electromyography study detected short motor unit potentials of myogenic pattern with abundant fibrillations and positive sharp waves. Whole-body MRI detected high intensity signals in the muscles of the shoulder girdle, proximal limbs, and thoracoabdominal trunk on short-tau inversion recovery sequence images. We diagnosed her as anti-PL-7 myopathy. After treatments with steroid, immunosuppressant, and immunoglobulin, her symptoms improved and abnormal MRI signals were normalized. Although MRI is known to be useful for detection of asymptomatic muscular inflammation in myositis, thoracoabdominal muscles are generally not covered in routine evaluation. To our knowledge, ours is the first case to detect acute inflammation of the thoracoabdominal muscles in antisynthetase syndrome. The present study suggests that whole-body MRI is useful for comprehensive evaluation of muscular involvement and longitudinal assessment for treatment outcomes.

Dopaminergic influences on risk preferences of Parkinson’s disease patients

Clinicians are increasingly recognizing impulse control disorders (ICDs) as a complication of dopaminergic treatment in Parkinson’s disease (PD). Considering the pivotal role of dopamine in reward information processing, ICDs may originate from dysregulation of reward-oriented behavior, and the behavioral changes may be reflected in shifts of psychological risk preference during decision-making. We used a behavioral economics paradigm to evaluate quantitatively the risk preferences of PD patients in levodopa on and off states. We also examined age-matched healthy controls. We found that levodopa increased the subjective value and prolonged the decision time in PD patients. These effects are apparently not explained by kinematic improvements but are attributed to psychological shifts of risk preferences and increased attention during risky decision-making. The risk preferences of healthy controls were similar to those of PD on levodopa treatment. The risk preferences of PD patients were not correlated with the scores of routine cognitive batteries, suggesting that dopamine-sensitive risk preferences are independent of cognitive capacities as measured by conventional batteries, including general intelligence, memory, and frontal functioning. By contrast, apathy and ICD partially predicted the risk attitude in PD patients, suggesting a common background of limbic origin behind these properties. The present results demonstrated that dopamine deficiency in off-state PD leads to risk-avoiding behavior and levodopa treatment increases the risk preferences. Behavioral economics framework is useful to evaluate short-term psychological changes in response to levodopa in PD patients.

T119. Strength of peripheral nerve stimulation impacts on the magnitude of synaptic plasticity induced at spinal motoneurons

Introduction Paired-associative stimulation (PAS), repeated transcranial magnetic stimulation (TMS) pairing with electrical peripheral nerve stimulation (ES), is one method of synaptic plasticity induction. If these two stimuli are delivered at the timing that descending volleys overlap with peripheral inputs at the spinal motoneurons (SM), long-term potentiation (LTP) like plasticity is induced at the SM synapses (SM-PAS). Here we investigated influences of stimulus intensity of ES on the degree of plasticity. Methods Eight right-handed healthy volunteers participated in this study. Electromyograms were recorded from right first dorsal interosseous muscle (FDI). Peripheral ES was delivered on right ulnar nerve at the wrist. TMS was applied over the left primary motor cortex (M1) hand area, and stimulus intensity was set at 120% resting motor threshold of the right FDI. We measured motor-evoked potentials (MEP) and F-wave latencies in each subject. As for SM-PAS, TMS and ES were delivered at the timing that antidromic volley derived by ES arrives at the postsynaptic terminals 1 ms before an initial descending volley evoked by TMS reaches the presynaptic terminals. A stimulus pairing of TMS with ES was given every 5 s (0.2 Hz) for 15 min (total of 180 pairs). Three different ES intensities were delivered at supramaximal intensity, at three times the sensory threshold (with muscle twitch), and at two times the sensory threshold (without muscle twitch). For evaluating SM synaptic excitability, single-pulse TMS was delivered at cervicomedullary junction level during brief contraction of the right FDI, and cervicomedullary MEP (CMEP) was recorded before and 1 min and every 10 min from 10 to 60 min after the SM-PAS intervention. Results CMEP increased after SM-PAS at supramaximal ES and at three times the sensory threshold, while SM-PAS at two times the sensory threshold induced no CMEP changes. SM-PAS with supramaximal ES was most effective. Conclusion SM-PAS at three times the sensory threshold induces sensory-motor associative plasticity constituted of sensory afferent inputs with multiple corticospinal descending volleys. Supramaximal ES stimulates both sensory afferent fibers and motor neuron axons antidromically, and SM-PAS may induce both sensory afferent and motor antidromic input associative plasticity. Antidromic inputs driven by supramaximal ES may augment associative synaptic plasticity at spinal motoneurons.

A case of leptomeningeal melanomatosis with acute paraplegia and multiple cranial nerve palsies

A 62-year-old man with acute paraplegia was transferred to our hospital. He had flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no meningeal irritation signs. MRI of the spinal canal showed swellings of the conus medullaris and the cauda equine, and also contrast enhancement of the spinal meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment. The lymph node was swollen in his right axilla. The biopsy specimen from the right axillary lymph node revealed metastasis of malignant melanoma histologically. Careful check-up of his whole body found a malignant melanoma in the subungual region of the right ring finger. Repeated cytological examination revealed melanoma cells in the CSF, confirming the diagnosis of leptomeningeal melanomatosis. His consciousness was gradually deteriorated. His family members chose supportive care instead of chemotherapy or surgical therapy after full information about his conditions. Finally, he died 60 days after transfer to our hospital. This is a rare case of leptomenigeal melanomatosis presenting with acute paraplegia and multiple cranial nerve palsies. Careful follow-up and repeated studies are vital for the early diagnosis of leptomenigeal melanomatosis in spite of atypical clinical presentation.

Contrast medium injection into the spinal cord

Contrast medium injection into the spinal cord Akioh Yoshihara, Sachiko Namatame, Nozomu Matsuda and Yoshikazu Ugawa Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima City, Fukushima, Japan, Department of Neurology, Ohara General Hospital, Fukushima City, Fukushima, Japan, and Fukushima Global Medical Science Center, Advanced Clinical Research Center, Fukushima Medical University, Fukushima City, Fukushima, Japan

Marked red nucleus lesions in metronidazole‐induced encephalopathy

An 84-year-old man presented with dysarthria. He had been taking 1.5 g/day metronidazole for a pulmonary abscess for a month. On neurological examination, the patient exhibited slurred speech and ataxic gait. His cranial nerves were intact, and his muscle tone, strength and sensation were normal in the extremities. Mild terminal oscillations were observed during finger-to-nose and heel-to-shin maneuvers. Magnetic resonance imaging (MRI) showed symmetric highintensity lesions of the cerebellar dentate nuclei, midbrain tectum, red nucleus and splenium of the corpus callosum on fluid-attenuated inversion recovery images (Fig. 1a). Notably, red nucleus lesions were swollen in this case. However, there was neither oculomotor palsy nor marked ataxia of the limbs corresponding to these MRI lesions. Diffusionweighted images showed high intensity in the corpus callosum, but the apparent diffusion coefficient value was not low (Fig. 1b). T2* images showed no hemorrhagic changes. After discontinuation of metronidazole, the symptoms improved, and the MRI obtained 12 days after initial imaging showed rapid disappearance of the lesions except for those in the splenium (Fig. 1c). MRI findings of metronidazole-induced encephalopathy is characteristic, and the red nucleus is occasionally involved. Because it is a reversible condition, physicians must be aware of the imaging features of metronidazole-induced encephalopathy. Acknowledgments