Toshiyuki Yanagisawa

Internal ophthalmoplegia with anti-GQ1b IgG antibody.

Sirs: Bickerstaff ’s brainstem encephalitis (BBE) is characterized by acute ophthalmoplegia and cerebellar ataxia preceded by infection. While generally considered a variant of Guillain-Barré syndrome, Fisher syndrome (FS) is believed by some neurologists to involve the brainstem [1]. Owing to the apparent similarities in the clinical presentations of FS and BBE, opinions differ as to whether the two syndromes are distinct or related, and to whether the causative lesions occur in the peripheral or central nervous system. Patients with BBE do exhibit symptoms and signs of central nervous system involvement, such as somnolence, brisk reflexes, or abnormal plantar response. High titers of anti-GQ1b IgG antibodies are detected in patients with BBE as well as in those with FS and Guillain-Barré syndrome [3, 9]. While the fact that BBE and FS share a common autoantibody suggests that they are closely related conditions, the final diagnoses must be based on clinical signs. The antiGQ1b IgG antibody is closely associated with acute paresis of extraocular muscles. This GQ1b ganglioside is highly enriched in the paranodal regions of the extramedullary portion of the oculomotor, trochlear, and abducens nerves [3]. Here, we report a case of BBE in which the initial symptom was photophobia, the first such case to be reported. Our patient showed minimal limitation of ocular movement, but her serum contained the anti-GQ1b IgG antibody.We performed a pharmacological study of the pupils, and here discuss the lesion likely to be responsible. A 53-year-old woman experienced sneezing and nasal discharge, which improved over the course of two days. She reported right ocular pain and exhibited reddish eruptions on her arms caused by consumption of milk or eggs and a nettle rash resulting from cold stimulations like water on the skin. Two days after the resolution of sneezing and nasal discharge, she noted hyperesthesia on her face and throat when contacted by cold wind or water. On the following day, she developed photophobia, diplopia, headache, and vomiting (day 1). She was admitted on day 6. The patient demonstrated alertness and normal mental functions. Her pupils were isocoric, both 7.0 mm in diameter, with minimal impairment of the upward gaze. The other directions of ocular movement were not limited. Light and accommodation reflexes were absent. There was no weakness in the extremities. There was slightly increased tonus in the muscles of both legs as well as mild truncal ataxia, and the deep tendon reflexes were symmetrically increased.Neck stiffness was not present. There was no impairment of pinprick, touch, position sense, or vibratory sensation. Autonomic nervous function was normal, as were the results of routine hematological and blood chemical tests. The cerebrospinal fluid protein was 23 mg/dl (normal 15~45 mg/dl) with 4 mononuclear cells/ l (normal < 5/ l).Viral screening of blood and CSF (including screening for the herpes simplex virus and cytomegalovirus) was unremarkable. MRI of the brain and spinal cord showed no abnormalities. An electroencephalographic examination also failed to show abnormalities. Auditory brainstem responses, nerve conduction studies, and Fwave responses were all normal. The patient was treated with acyclovir and methylprednisolone. An enzyme-linked immunosorbent assay showed that the serum IgG obtained on day 6 reacted strongly with GQ1b (1:64000), but not with GM1, GM2, GD1a, GalNAc-GD1a, GD1b, GD2, or GT1b. The patient was prescribed 1000 mg of methylprednisolone on days 7, 8, 9, 21, 22, and 23. Her food allergies disappeared after the first steroid pulse. On day 45, the left pupil responded to light, contracting from 7.0 mm to 6.0 mm. Two months after the onset of neurological signs, the anti-GQ1b IgG antibody titer became 1:16000. Tendon reflexes remained increased, and mydriasis persisted, with the left pupil smaller and slightly oval in shape. A limited pupillary light reaction and near response were present bilaterally, more marked on the right side. Ocular gaze limitation diminished,and the diplopia gradually improved (Figure). Results of pharmacological tests involving the patient’s pupils two months after onset were as follows: pilocarpine 0.125 % caused pupillary constriction from 7.0 mm to 4.0 mm on the right and from 6.0 mm to 3.0 mm on the left; 1.25 % epinephrine caused slight dilation from 6.0 mm to 7.0 mm on the right, and from 5.0 mm to 7.0 mm on the left; while 5 % cocaine also caused dilation from 6.0 mm to 7.0 mm on the right, and from 5.0 mm to 6.0 mm on the left. Five months after the onset of symptoms, the ocular gaze limitations and diplopia had almost disappeared, but other neurological signs persisted. The anti-GQ1b IgG antibody titer became 1:8000. The main clinical feature of our patient was the presence of bilateral LETTER TO THE EDITORS

Rest-induced suppression of anterior horn cell excitability as measured by F waves: Comparison between volitionally inactivated and control muscles

To test the hypothesis that the anterior horn cells become hypoexcitable in the absence of central drive, we recorded F waves simultaneously from the first dorsal interosseous (FDI) and the abductor digiti minimi (ADM) before and after volitionally inactivating one muscle (target) while periodically contracting the other muscle (control). In 14 healthy subjects, F waves recorded from the target muscle showed a progressive decrease in persistence and amplitude (whether counting all 100 trials or only detectable responses) after muscle relaxation for 1, 3, and 6 hours, followed by a quick recovery upon brief muscle contraction. We conclude that volitional inactivation suppresses the F waves of the target muscle without equally affecting the control muscle innervated by the same nerve. The history of activity of a muscle should therefore be taken into account in clinical testing, especially when the study of a paretic muscle shows abnormal F‐wave excitability. Muscle Nerve, 2007

Natural course of combined limb and palatal tremor caused by cerebellar‐brain stem infarction

After infarction of the left superior cerebellar peduncle and dentate nucleus, a patient developed tremor of the left upper limb beginning on the twelfth day followed by palatal tremor appearing 10 months after infarction. Surface electromyogram revealed a difference in the frequency of the tremor in the upper limb and soft palate. When the palatal tremor appeared, brain magnetic resonance T2‐weighted images revealed high signal intensity of the contralateral, right inferior olivary nucleus. Subsequently, when the amplitude of palatal tremor became less severe, the high olivary signal intensity subsided whereas the hypertrophy of the nucleus remained. This patient provides useful information on the pathogenesis of skeletal and palatal tremor with brain stem or cerebellar lesions based on the differences in the onset and frequency of tremors and morphologic changes in the inferior olive.

A case of rhabdomyolysis in which levetiracetam was suspected as the cause

Several studies have reported rhabdomyolysis induced by various drugs but not by the antiepileptic drug levetiracetam. We present a case of suspected levetiracetam-induced rhabdomyolysis. A 29-year-old woman was hospitalized for generalized tonic–clonic seizure and given levetiracetam for the first time. One day after starting levetiracetam, she developed myalgia, particularly backache, and weakness in both lower limbs. Based on her clinical symptoms and blood test results indicating hyperCKemia, our diagnosis was levetiracetam-induced rhabdomyolysis. Withdrawal of levetiracetam immediately improved the clinical symptoms and hyperCKemia. This first report of suspected levetiracetam-induced rhabdomyolysis provides important information for treating patients early in levetiracetam administration.

89. Long-term efficacy of repetitive transcranial magnetic stimulation for cortical cerebellar atrophy

The aim of this study was to decide an adequate parameter to evaluate interference pattern in needle electromyography quantitatively. We usually evaluate interference pattern by semiquantitative evaluation to 4 from 1;‘4’ is the state that base line is full of motor unit, and‘1’ is only one or two motor units. In this study, we compared semiquantitative evaluation and four quantitative parameters: ‘Activity’, ‘Peak counting’, ‘Integral value’ and ‘Average amplitude’, and considered which parameter was useful. We defined Activity as a ratio more than the threshold of ±50 V. We examined 46 muscles, in which 25 muscles had neurogenic changes, of seven patients who was necessary to take needle electromyography. We used concentric needle electrode for examination. As a result, four parameters showed high correlation between semiquantitative evaluation. A correlation coefficient was highest in Activity: Activity 0.898; Peak counting 0.833; Integral value 0.624; Average amplitude 0.728. Activity was useful when we evaluated semiquantitative evaluation 4, Peak counting was useful in evaluation 1 or 2 more in detail. It is particularly useful in muscle of a neurogenic change.

Brain atrophy in patients of amyotrophic lateral sclerosis after long-term survival with tracheostomy positive pressure ventilation

1) Kimura F. Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis. Clin Neurol 2016;56:241-247. 2) Kawata A, Mizoguchi K, Hayashi H. A nationwide survey of ALS patients on tracheostomy positive pressure ventilation(TPPV) who developed a totally locked-in state(TLS) in Japan. Clin Neurol 2008;48:476-480. 3) Mezzapesa D.M, Ceccarelli A, Dicuonzo F, et al. Whole-brain and regional brain atrophy in amyotrophic lateral sclerosis. Am J Neuroradiol 2007;28:255-259. 4) Mori H, Yagishita A, Takeda T, Mizutani T. Symmetric temporal abnormalities on MR imaging in amyotrophic lateral sclerosis with dementia. Am J Neuroradiol 2007;28:15111516.  Artificial respiratory support is an important option of respiratory management for amyotrophic lateral sclerosis (ALS).  By this support the surviving rate of ALS patients had increased1),2). Therefore, it has been recognized that most patients occurs brain atrophy after long-term survival.  We had an opportunity to observe brain computer tomography (CT) of long surviving ALS patients with tracheostomy positive pressure ventilation (TPPV).

経鼻胃管挿入者にみられる両側声帯麻痺：nasogastric tube syndrome 4例の検討

We report 4 cases of elderly patients with abrupt onset of serious airway obstruction that is presumed to be due to indwelling nasogastric tube. 2 cases are patients of cerebral infarction and 2 cases are patients of Parkinson disease. The average number of days until NGTS is 17.8 days. In all cases, fiber-optic examination revealed complete loss of adduction in both vocal cords. Infection in the posterior cricoid region caused by ulcerative lesions at the upper end of the esophagus has been implicated as a pathophysiological mechanism of this syndrome, but it was not possible to confirm in the 4 cases. Because it is difficult to exactly diagnose with NGTS in clinical practice, there is a need to consider the inducing factor and response. Body mass index is very low in each of the 4 cases, ranging from 14.2 to 18.0, implying a severely malnourished or immunocompromised state, and may represent a high risk factor for this syndrome. Whenever this life-threatening syndrome is suspected, direct vocal cord examination and removal of the tube are recommended. In addition, the clinicians should not hesitate about doing intubation or tracheotomy in emergency.

P23-10 The risk factor of arteriosclerosis in hemifacial spasm patients evaluated by magnetic resonance imaging and brainstem auditory evoked potential

Objective: To investigate to which extent posterior auricular muscle (PAM) was affected in hemifacial spasm accompanied by auricular symptom and the role of botulinum toxin A injection in the PAM. Methods: There were 265 consecutive HFS patients between July, 2009 and January, 2010; And 63 patients who met the inclusion criteria were enrolled. 33 of 63 patients were given the standard treatment plan of botulinum toxin A (conventional group), 4 units of botulinum toxin A was injected to PAM to 30 patients in addition to the routine HFS treatment plan (PAM group). Before injection, the blink reflex activity and lateral spread of blink reflex to orbicularis oris and PAMs were recorded; Clinical and electrophysiological studies were reviewed at least 4 weeks later (29.47±2.53 days) at the follow-up visit. Results: (1) Compared with those before injection, partial patients of both groups reported that their previous auricular symptoms subsided, the remission rate were 45.5% (15/33), 76.7% (23/30) respectively, the symptoms of PAM group subsided better (c2 = 6.40, P = 0.011). (2) Compared with those before injection, the AMR amplitudes of PAM (390.00±53.58) vs (72.00±9.67), t = 6.011, P = 0.000; and orbicularis oris (405.33±66.71) vs (106.67±10.54), t = 4.383, P = 0.001; of both groups decreased, the AMR amplitudes of PAM in PAM group decreased more obviously (t = 4.237, P = 0.001). There is no obvious difference on the AMR amplitudes of orbicularis oris between both groups (t = 1.127, P = 0.269). Conclusions: Electrophysiological study contributes to the treatment in patients who developed auricular symptoms on the symptomatic side; Those patients may benefit from botulinum toxin injection in the PAM in addition to the routine HFS treatment plan.

F wave as a measure of selective suppression of the anterior horn cells involving only the volitionally inactivated muscle

Bulbar and spinal muscular atrophy (BSMA) is an adult onset motor neuropathy with androgen receptor gene mutation of expanded CAD repeat. But sensory function has been considered to be a little abnormality of vibration sense on a clinical basis. There are several pathologic reports indicating that peripheral sensory fibers are involved in BSMA. To evaluate changes in sensory nerve function quantitatively, we measured nerve conduction study (NCS) of the median, ulnar, peroneal, tibial and sural nerve, and motor deficit with Norris scale and ALSFRS in 72 patients (52.6 ± 9.3 years) with BSMA. In BSMA, amplitude and nerve conduction velocity of CMAP and SNAP was significantly smaller than in normal controls (p < 0.001). Appearance ratio of F wave in upper lib is significantly smaller than in normal controls (p < 0.001). 12.5% and 2.8% of SNAP in sural and ulnar nerve was not evoked. CAG repeat, motor severity and duration of disorder were not correlated with NCS. The Norris scale divided by age is significantly correlated with SCV and amplitude in sural nerve. So sensory nerve abnormality is important parameter in clinical aspect of BSMA.

Therapeutic efficacy of transcranial magnetic stimulation for amyotrophic lateral sclerosis and spinocerebellar degeneration

Abstract We treated four patients with amyotrophic lateral sclerosis (ALS) and nine patients with spinocerebellar degeneration (SCD) using transcranial magnetic stimulation (TMS) with an SMN-1200 transcranial magnetic stimulator. The stimulus strength was below 1.5 T and the interpulse interval was greater than 5 s. The stimulus coil was placed on P3, P4 and the bilateral cervical and lumbar root in the ALS patients, and tangentially over Iz, 4 cm lateral to the right from Iz and 4 cm lateral to the left from Iz in the SCD patients. Ten consecutive pulses were delivered to each region in the ALS patients and 15 in the SCD patients. Transcranial magnetic stimulation (TMS) was applied for a total of 20 days for in-patients and once or twice a week as ongoing therapy for outpatients. Patients with ALS were assessed according to the Barthel index, and a respiratory function test was performed before and after TMS. Patients with SCD were neurologically assessed according to the International Cooperative Ataxia Rating Scale (ICARS). In addition, the patients were evaluated for regional cerebral blood flow (rCBF) by 99 m Tc-ECD SPECT using a modified Patlak-plot method before and after the TMS trial. No change in the Barthel index or rCBF was observed in patients with ALS. The respiratory function test results improved in one patient in the ALS group. The ICARS rating of seven patients with SCD improved after TMS. The rCBF of patients with SCD in the bilateral cerebellar hemispheres was significantly faster compared to their flow rate before TMS. These data suggest the potential usefulness of TMS as a therapeutic tool for ALS and SCD.