Comparison of therapeutic efficacies of type A and F botulinum toxins for blepharospasm: a double-blind, controlled study.

Type F botulinum toxin can be used for treating patients with dystonia who become refractory to type A toxin injection due to antibody development. We compared the therapeutic efficacy of type F botulinum toxin to that of type A toxin in a self-controlled, double-blind clinical trial. In nine patients with blepharospasm, we injected type A toxin on one side and the same units of type F toxin on the other side. Although the onset of clinical effect, maximal benefit, and adverse reactions were similar between type A and F toxins, the duration of the clinical effect was significantly shorter on the side injected with type F toxin. Although type F toxin proved its promise as an alternative to type A toxin, its usefulness is limited by the shorter duration of action.

von Recklinghausen disease complicated by pulmonary hypertension.

Two patients with von Recklinghausen disease (neurofibromatosis type 1) were admitted to the hospital because of progressive heart failure. Both patients had prominent pulmonary hypertension revealed on cardiac catheterization. A lung perfusion scan did not show any gross defect. There were no underlying causes of pulmonary hypertension in either patient, such as chronic lung disease, congenital or acquired heart disease, deep vein thrombosis, or systemic hypercoagulable states. There may be an unrecognized association between von Recklinghausen disease and pulmonary hypertension.

DYT1 mutation in Japanese patients with primary torsion dystonia.

A GAG deletion at position 946 in the DYT1 gene has been identified as one of the gene mutations responsible for autosomal dominant primary torsion dystonia. We examined 178 Japanese patients with various forms of dystonia, and found the mutation in six patients (3.4%) from three families. Five of them had early clinical onset (before age 12) with initial involvement of a limb. To our knowledge, this is the first report of the frequency and the clinical features of DYT1 mutation in oriental patients, and the clinical presentation of the mutation in these patients was similar to that of Jewish or non-Jewish Caucasian patients.

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3.

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis.

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.

[Botulinum toxin trial for spasticity].

We treated three patients with spastic paraparesis with botulinum toxin (BTX). Two of them had scissors gait reflecting the hypertonus of adductors. In both, an injection of BTX to the responsible muscles improved gait, albeit transiently. The effect was shortlived, probably because increased tonus in non-injected portions compensated for the weakness of injected portions. In the third patient with no abnormality in tonus of the adductors, BTX injection in quadriceps caused a weakness with exacerbation of gait disturbance. We concluded that, in selected cases, BTX therapy is useful for spastic paraparesis to alleviate hypertonicity of the adductors.

[Left-sided extremity myorhythmia and rightward slow eye movement caused by a hemorrhage in the right pontine tegmentum].

A sixty-year-old man was admitted to our hospital on January, 1989. He had suffered a hemorrhage in the right side of pontine tegmentum on April, 1988. He had been in deep coma for about a week, and then he had showed diplopia, mild right deafness, right facial palsy, left hemiparesis, dysarthria, dysphagia, and urinary disturbance. He showed slight improvement of these symptoms and signs, but had developed thereafter extremity myorhythmia on the left side. On admission, rightward slow eye movement (absence of saccadic eye movement and preservation of pursuit eye movement of both eyes) was present. MRI revealed a hypointensity lesion with a hyperintensity spot on T2-weighted images showing an old hemorrhage in the right pontine tegmentum and a hyperintensity lesion on T2-weighted images showing an olivary pseudohypertrophy on the right. We concluded that the extremity myorhythmia in this patient was caused by the damage of the right central tegmental tract followed by right olivary pseudohypertrophy. The rightward slow eye movement was considered to be due to the damage of the right paramedian pontine reticular formation and/or its afferent fibers in the pontine tegmentum.

[Intravenous immunoglobulin therapy in multifocal motor neuropathy].

We treated ten consecutive patients with multifocal motor neuropathy (MMN) with high-dose intravenous immunoglobulin. Ages ranged 18 to 58 years, with disease duration of 9 months to 8 years. We treated them with 0.2 g/kg of human immunoglobulin for 6 consecutive days. All but one showed a clinical improvement starting within a week after the first infusion. The functional improvement ranged from marked to mild degree. In six patients, the clinical effect abolished within 2 months. Improvement was persistent for more than 6 months in the other three. In only two patients conduction block improved after the treatment. The discrepancy may result from an increased threshold of remyelinated or chronically demyelinated fibers for excitation. Side effects were not documented. This pilot study indicates that immunoglobulin may be a safe and effective therapy for MMN.

[Treatment of Guillain-Barré syndrome with "axonal" involvement by plasma exchange].

A 19-year-old man with Guillain-Barré syndrome (GBS), who had been bedridden, dramatically improved after plasma exchange despite electrophysiological evidence of severe axonal damage. We commenced the therapy at 24 days after the onset of illness. Each trial of plasma exchange improved the strength clinically and rapidly increased the amplitude of the compound muscle action potential. Four months later, muscle strength recovered to normal except for mild weakness of the distal limb muscles. The time course of such a prompt recovery precludes axonal regeneration as its underlying mechanism in our patient. We postulate that some humoral factor might have reversibly depressed the axonal excitability, causing clinical symptoms which mimic axonal degeneration. Plasma exchange is a choice of treatment even for patients with GBS showing electrophysiological findings suggestive of axonal involvement.

[Multifocal demyelinating polyneuropathy with persistent conduction block (Lewis-Sumner syndrome)].

Multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome) is a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which often clinically simulates a motor neuron disease (MND). We report here three patients initially suspected to have MND, who later were diagnosed as a Lewis-Sumner syndrome. One of them showed a remarkable clinical improvement after immunoglobulin therapy. The definitive diagnosis of this syndrome rests upon nerve conduction studies, uncovering multiple sites of persistent conduction block. Technically, it is important to exclude insufficient stimulus which may lead to an erroneous impression of conduction block. Magnetic stimulation, as compared to electric current, elicited larger responses possibly because of deeper current penetration. We found this mode of stimulation useful especially in testing focal demyelination requiring full activation of a diseased nerve at a most proximal segment.

[Changes of autonomic functions by endoscopic upper thoracic sympathectomy on idiopathic hyperhidrosis].

Changes of autonomic functions before and after bilateral endoscopic upper thoracic sympathectomy (EUTS) were evaluated in 13 patients with idiopathic hyperhidrosis, with the sympathetic skin response, coefficient of variation of R-R intervals, mean heart rate, thermography, and non-invasive Valsalva test of the tonometry method. EUTS electronically destructs the upper thoracic sympathetic ganglions which innervate the upper extremities, and partially the heart. The decrement of mean heart rate, and persistent inhibition of the vascular contraction and hidrosis of the hands appeared after EUTS. These manifestations were effect produced by the abortion of sympathetic activity by EUTS. In 10 of the 12 cases, the baroreceptor sensitivity index II of Valsalva test which reflects the sympathetic autonomic nervous function of the heart showed normal pattern after EUTS. Four cases revealed reincrement of both the blood pressure and heart rate at the latter half phase of the second stage of the Valsalva test. The sympathetic dysfunction of the heart was limited to the decrement of mean heart rate although EUTS partially destroys sympathetic fibers innervating the heart. A long-term study is necessary to evaluate the effect of EUTS on the cardiac function.

[Internal carotid artery occlusion related to seat belt shoulder strap: report of two cases].

Two cases of traumatic internal carotid artery occlusion probably related to the seat belt shoulder strap are reported. Case 1. A 20-year-old woman was driving and was struck on the right front side of her car by another car. There were neither bruises, abrasions on her neck, nor weakness in her extremities. About 4 hours later, she developed left hemiplegia, and CT scan taken on the following day revealed low density areas in the capsulostriatal area on the right. The right carotid angiography revealed occlusion of the internal carotid artery about 3 cm distal to the bifurcation. Case 2. A 43-year-old man was driving and was struck on the front of his car by a hard iron railing. He sustained a sternum fracture, but there was no disturbance of consciousness or paresis of the extremities. His neck was unremarkable externally. About 50 days later, he developed left hemiplegia. CT scan and MRI revealed a massive infarction in the distribution of the right middle cerebral artery territories. The carotid angiography revealed occlusion of the right internal carotid artery about 3 cm distal to the bifurcation. In each cases, the driver was wearing a three-point shoulder seatbelt when the car was struck on the front or on the right front. Previous experimental studies have revealed in these situations the neck is flexed right anteriorly, and then quickly overextended left posteriorly. The overextension of the neck probably injured the intima of the internal carotid artery ipsilateral to the shoulder fixed in the seatbelt, resulting in the subsequent occlusion by a thrombus.

[Treatment of spasticity with botulinum toxin and muscle afferent block].

Spasticity is partly caused by disinhibition of spinal stretch reflex activity and blocking of the group Ia afferents may improve its clinical symptoms. Since muscle afferent block has been successfully used for treating dystonia, this method may become useful for treating spasticity as well. We injected diluted lidocaine (0.5%, 50 ml/session) and ethanol (5 ml) into thigh adductors (for leg crossing), medial hamstrings (for medial rotation of the leg), quadriceps femoris (for hyperextension of the knee), tibialis posterior and triceps surae muscles (pes equinovarus deformity), biceps brachii and forearm flexors (for flexion deformities of the upper extremity) in 12 patients with spasticity. Although the duration of action was short (< 1 day) at first, it was gradually prolonged to several weeks by repeating the injection every 3-4 days. The final outcome was comparable to that obtained by botulinum toxin injection in the same group of patients. This method may prove its promise as a means of treating spasticity.

[Memory dysfunction of spinocerebellar degeneration].

We evaluated Rey's auditory verbal learning test (AVLT) and Wechsler adult intelligence scale (WAIS) in 29 patients with spinocerebellar degeneration (SCD) younger than 65 years old. They showed a significant impairment in the recall subtest of AVLT. However in the recognition subtest, there was no significant impairment in the recall subtest of AVLT. However in the recognition subtest, there was no significant difference between the patients and the control subjects. The patients with SCD also showed a significant decrement in both VIQ and PIQ. The disturbance of recall memory did not correlate with the disturbance of VIQ. The disturbance of recall memory without that of recognition memory is considered to be a characteristic of subcortical dementia. Therefore we concluded that the patients with SCD may develop subcortical dementia and that the localization of the disturbance of recall memory and that of the disturbance of VIQ might be different.

[123I-IMP SPECT findings of visual perseveration in a patient with old hemorrhage in the right occipital lobe].

We report a case of visual presevertation in a 67-year-old man. He had been well until 66 years of age when he had brain hemorrhage in the right occipital lobe. After an operation for removal of the hematoma, visual hallucination occurred and persisted for about 6 months. One year and a half later, he had a convulsive seizure and diphenylhydantoin was started. During the two weeks following the convulsion, he several times experienced episodes of visual preservation, visual hallucination and metamorphopsia. MRI revealed an old hemorrhage in the right occipital lobe. 123I-IMP SPECT demonstrated increase of cerebral blood flow of the right medial occipital lobe one day after the episode of visual perseveration and decrease about three weeks after the episode. The mechanism which causes visual perseveration still remains to be clarified. The findings of 123I-IMP SPECT of the present case suggest that visual perseveration may be generated by postictal transient functional excitation of the right occipital lobe.

[Cervical echomyography in cervical dystonia and its application to the monitoring for muscle afferent block (MAB)].

Muscle afferent block (MAB) is an intramuscular injection of 0.5% lidocaine and pure ethanol with a volume ratio of 10:1, introduced as an alternative to botulinum toxin injection for focal dystonia and spasticity. As in the case of botulinum toxin injection, the precise localization of target muscles is crucial to obtain the maximal effect from MAB. For this purpose, we performed ultrasonography of cervical muscles (echomyography) in 20 patients with cervical dystonia (11 men, 9 women; mean age 46.1), with ultrasonograph SSD-5500 (Aloca Co. Ltd., Japan) and a 7.5 MHz linear probe. In untreated subjects, the boundaries of muscles could be easily identified, while they tended to become ambiguous after repeated MAB sessions. At rest, there were involuntary worm-like movements of a specific muscle group observed in all patients. Contrary to our expectation, in all but one patient abnormal contraction was limited only in a part of synergists responsible for the abnormal posture. In normal subjects there was no abnormal contraction at rest, and all the synergists were simultaneously activated by the voluntary neck deviation. Normal subjects could not mimick the pattern of muscle activity in dystonic patients. The echo-guided MAB was performed in 16 patients. We could easily observe the diffusion of lidocaine and ethanol into the targeted muscle, and injected portions of the muscle stopped their activities just after MAB. The effect persisted for 3-4 days in at least 5 out of 10 patients who had follow-up examination. On the other hand, the movement stopped only temporarily after the injection of saline or lidocaine only. In 3 out of 16 patients, some of the uninjected synergists were activated as if to substitute for the treated muscle just after the injection. We conclude that cervical echomyography is useful to investigate the pattern of muscle activity in cervical dystonia and to accurately localize the contracting muscles during MAB.

[A case report of pyomyositis--early diagnosis and follow-up by MRI].

We report a rare case of pyomyositis in a 28-year-old Japanese woman who was not immunocompromised. She was admitted because of high fever, sore throat, and severe tenderness and swelling of the right calf. Redness, swelling, and tenderness indicated presence of acute inflammation in the calf. CT of the lower extremities demonstrated low density areas in the right soleus muscle and surrounding fascia with marked swelling, which were of high signal on T2 weighted images of MRI. There was no finding of abscess formation. A tentative clinical diagnosis of acute pyomyositis was made, and antibiotics therapy with a combination of fosfomycin and sulbactam/cefoperazone was started although the arterial blood culture was negative for bacteria. Associated acute tonsilitis was the most probable focus of pyomyositis. Antibiotics relieved her symptoms, and the inflammation subsided in several weeks. No surgical procedure was necessary. MRI taken tree weeks after the onset demonstrated abscess formation between the soleus and gastrocnemius muscles. Slight high intensity indicating scar formation remained in the area of the former abscess six weeks after the onset. MRI was very useful not only in making the early diagnosis but also in the follow-up of pyomyositis.

[Treatment of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)--a review].

This is a review article about the recent progress and the general consensus of the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the first line treatment is believed to be adrenocorticosteroid prescribed orally or intravenously, some insist that plasmapheresis or intravenous immunoglobulin is better. The latter two are expensive but the effects are comparable to that of steroid, and in some patients complete remission might be induced. On the other hand, about 30% of patients do not respond to any of these conventional procedures, and for these the combination of two or three of them might be effective. As another choice, immunosuppressant or interferon (alfa-2 a or beta-1 a) has been applied although its usefulness is still inconclusive. For any of these here mentioned, the clinical response greatly varies among patients, and the elucidation of predictive factors of effectiveness is eagerly awaited from the standpoint of reasonable treatment selection and cost-effectiveness.

[Treatment of hemifacial spasm with type A botulinum toxin (AGN 191622): a dose finding study and the evaluation of clinical effect with electromyography].

Forty-one patients with hemifacial spasm had an injection of type A botulinum toxin (AGN 191622; Allergan Co. Ltd., Irvine, CA). Patients were randomly divided into 3 groups by the injection dose: group L (1 unit; 14 patients), group M (5 units; 14 patients), and group H (10 units; 13 patients). Half of the dose was injected into the orbicularis oculi and the rest into the zygomaticus major muscles on the affected side. The clinical effect and electromyogram were evaluated at 2 weeks after the injection. The clinical benefit was dependent on the injection dose, and group H showed the highest rate of improvement (84.6%). No adverse effect related to the toxin was demonstrated except one patient in group H who showed mild and transient lagophthalmos. For 81.8% of group H patients, the final judgement was "useful" or "very useful", which was 9.1% for group L and 50.0% for group M. On the other hand, electromyography disclosed no consistent dose-finding relationship. We conclude that at least 10 (preferably more) units of botulinum toxin are necessary for effectively treating hemifacial spasm. Electromyography has only limited value for the evaluation of clinical effect.

[Dose-response relationship in the treatment of cervical dystonia with botulinum toxin type A (AGN 191622)--a phase II study].

Injection of botulinum toxin type A has been the treatment of choice for spasmodic torticollis for several years. Although previous reports demonstrate its effectiveness and safety, the treatment strategy has been empirical. The present study, using the freeze-dried crystalline botulinum toxin type A (AGN 191622; Allergan Inc., Irvine, CA), aimed to compare the efficacy among three treatment groups divided into low, medium and high dosage levels. Fifty-one patients who entered the study were grouped into low-dose (60 units/session), medium-dose (120 units/session) and high-dose (240 units/session) groups. Two patients (one in low-dose group and the other in high-dose group) were excluded from the assessment of efficacy because they dropped out in the early phase of the study. One experienced worsening of an existing psychosis and the other developed an acute respiratory infection. Injection sites were decided individually by palpation. If the clinical response was not satisfactory four weeks after an injection, the patient was re-injected with the same dose of toxin. The follow-up period was 14 weeks from the initial injection. The results showed that the high-dose group improved more than the other groups in the parameters of severity of symptoms and subjective benefit (p = 0.000). Also, fewer injections were required in the high-dose group to achieve substantial clinical benefit. Although the mean reduction in Tsui's score was not statistically significant among the groups, the "marked improvement" was seen more frequently in the high-dose group (p = 0.033). Unfavorable adverse effects including excessive weakness and dysphasia were always mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)