Yasumitsu Ichikawa

Reduction in the motor unit number estimate (MUNE) after cerebral infarction

BACKGROUND The mechanism of the decrease in motor unit number estimates (MUNEs) after cerebral infarction has not been studied systematically. We examined the relationship between the degree to which MUNEs decreased and the other clinical features of patients with the infarction. METHODS Using a multiple point stimulation technique, we obtained the MUNE of the hypothenar muscle group in 13 age-matched control subjects and 30 patients with cerebral infarction. In all patients, we obtained the Japan Stroke Scale (JSS) and head MR images. In eight patients with acute cerebral infarction, admitted within 24 h after onset, we also obtained head MR angiograms and single-photon emission CT. FINDINGS There was a decrease in the MUNE of the hypothenar muscle group on the affected side of 24 patients with cerebral infarction and hand weakness. The decrease in the MUNE started from 4 to 30 h after the infarction, when T1-weighted MR images of the brain involved were normal. The degree to which the MUNE decreased correlated with the part of the JSS showing the upper extremity weakness. INTERPRETATIONS A decrease in the MUNE of the hypothenar muscle group within 30 h after cerebral infarction may be due to trans-synaptic inhibition of the spinal alpha motor neurons innervating this muscle.

Protective effect of interleukin- 3 and erythropoietin on motor neuron death after neonatal axotomy

Abstract Several members of hematopoietic factors are known to have neuroprotective effects against axotomized motor neuron death. We carried out a study to determine whether interleukin-3 (IL-3) and erythropoietin (EPO) rescue spinal motor neuron death following axotomy. Unilateral sciatic nerve was transected in neonatal rats. Different doses of IL-3, EPO, or vehicle were administered daily for two weeks by intraperitoneal injection. After treatment, the number of spinal motor neurons was determined at the level of L4 segment. In comparison with vehicle, both IL-3 (10 µg kg -1) and EPO (5.0 mg kg-1) significantly prevented the loss of motor neurons. Protective potentials is the same between them. These results suggest that IL-3 and EPO play a role for motor neuron survival in vivo and suggest the potential use of these hematopoietic factors in treating diseases that involve degeneration and death of motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis.

The diagnostic interval in amyotrophic lateral sclerosis

We studied whether there are any parameters that influence the period between onset of symptoms and confirmation of diagnosis in 117 patients with ALS (65 male, 52 female). The mean age of diagnosis was 57 years for men and 59 years for women. Bulbar-onset patients were older at diagnosis than limb-onset patients both men and women. Patients with bulbar-onset appeared to be more frequent in women (33:19). Contrariwise, limb-onset patients were more frequently male (43:22). The time to confirmation was much shorter with symptoms of bulbar-onset (10.5 months in male, 9.8 months in female) than for those with limb-onset (13.7 months in male, 14.8 months in female) in male, respectively, female ALS patients. The diagnosis of ALS was established in all cases by neurologists in our study.

Ulcerative colitis presenting as sensorineural deafness, brainstem encephalopathy, and white matter lesions.

Background:Several rare neurologic complications of ulcerative colitis have been reported. Review Summary:We report a 69-year-old Japanese woman who developed bilateral sensorineural deafness, 2 attacks of bilateral ophthalmoplegia, and bilateral facial nerve palsy in association with ulcerative colitis. Laboratory data showed elevated cerebrospinal fluid (CSF) protein without pleocytosis, abnormal auditory brainstem evoked potentials, and multiple high signal lesions on magnetic resonance imaging of the brainstem and cerebral deep white matter. Her symptoms improved with corticosteroid therapy except for sensorineural deafness and an exacerbation of cerebral deep white matter lesions without any new clinical signs. Conclusion:Immunologic mechanisms may have led to her central and peripheral nervous system findings in addition to her colon disorder.

Trophic effect of Olmesartan, a novel AT1R antagonist, on spinal motor neurons in vitro and in vivo

Abstract Olmesartan is a novel compound which has been shown to exhibit various neuropharmacological effects. For the purpose of clarifying the effect of Olmesartan on spinal motor neurons, we studied the following tests. We studied the effect in vitro of Olmesartan on neurite outgrowth and choline acetyltransferase (ChAT) activity in primary explant cultures of ventral spinal cord (VSCC) of fetal rats. Olmesartan-treated VSCC, compared with control VSCC, had a significant neurite outgrowth and increased activity of ChAT. The effect was dose-related in neurite outgrowth. However, there was no relationship between activity of ChAT and given doses of Olmesartan. We examined in vivo the effect of Olmesartan on axotomized spinal motor neuron death in the rat spinal cord. After post-natal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of Olmesartan for consecutive 14 days reduced spinal motor neuron death. There was no relationship between number of surviving neurons and doses of Olmesartan. These in vitro and in vivo studies showed that Olmesartan has a neurotrophic effect on spinal motor neurons. Our data suggest a potential therapeutic use of Olmesartan in treating diseases that involve degeneration and death of motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis. [Neurol Res 2002; 24: 468-472]

Vasoactive intestinal peptide influences neurite outgrowth in cultured rat spinal cord neurons.

Abstract Vasoactive intestinal peptide (VIP) is a neuropeptide which has been shown to exhibit a wide range of neurotrophic effects both in vivo and in vitro . For the purpose of clarifying the effect of VIP on spinal cord neurons, we studied the effect of VIP on neurite outgrowth of fetal rat ventral and dorsal portions of spinal cord in cultures. VIP-treated ventral spinal cord cultures (VSCC), compared with control VSCC, had a significant neurite outgrowth at 10-8, 10-6, and 10-4 M. The effect was considered to be concentration dependent. Morphological changes of the dorsal spinal cord cultures (DSCC) remained unchanged by VIP treatment. Because of their close sequence homology with VIP, PHI-27 (peptide, histidylisoleucine amide) and secretin were also examined with the same experimental conditions as was VIP. Both PHI-27 and secretin had neurite promoting effects in VSCC at 10-8 and 10-6 M, respectively. However, there were no neurite promoting effects in DSCC in both of them at any concentrations. VIP had the most potent effect on neurite outgrowth in VSCC, followed by PHI-27, and secretin in their effectiveness concentrations. Our data showing VIP, PHI-27 and secretin have neurotrophic action on VSCC and suggest that a potential therapeutic use of VIP and its related peptides in treating diseases that involve degeneration and death of spinal motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis. [Neurol Res 2001; 23: 851-854]

Pompholyx after IV immunoglobulin therapy for neurologic disease

To the Editor: We read with interest the article by Iannaccone et al.1 concerning pompholyx after IV immunoglobulin (IVIg) therapy for neurologic disease. They suggested that pompholyx occurred in 3 of their 23 patients with peripheral neuropathies. This eczema is one of several adverse events following IVIg treatment. In our evaluation of 5 patients with Guillain-Barre syndrome (GBS) and 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), they received standard IVIg therapy (0.4 g/kg/day for 5 consecutive days at a slow infusion rate of longer than 10 hours). Of those treated with IVIg, one patient with CIDP developed vesicular eczema 5 days after the last day of therapy. We suggest a relationship between high plasma IgG concentrations and pompholyx in such a patient and discuss eczema after IVIg therapy. A 72-year-old Japanese woman was diagnosed with recurrence of CIDP. She had a clinical history of carbamazepine-induced rashes. At 5 days postinfusion after IVIg (Glovenin-I) …

Neuroprotective actions of FK506 and cyclosporin A on motor neuron survival following neonatal axotomy

Abstract We show that nonimmunosuppressive analogues of the immunosuppressive drugs FK506 and cyclosporin A (CsA) rescue axotomized neonatal motor neuron death. Unilateral sciatic nerve was transected in neonatal rats. Animals were then treated daily with different doses of FK506 and CsA for 14 days with intraperitoneal injection. Control rats received phosphate buffer saline (PBS) in the same fashion. After treatment, the number of spinal motor neurons was determined at L4 level. In comparison with vehicle, both FK506 (5.0 mg kg-1) and CsA (10.0 mg kg-1) rescued motor neuron death in a similar way. These results indicate therapeutic relevance in the treatment of damaged motor neuron disorders, such as motor neuropathy or amyotrophic lateral sclerosis. [Neurol Res 2002; 24: 573-576]

T-588 enhances neurite outgrowth and choline acetyltransferase in cultured rat spinal ventral horn neurons.

T-588(R(-)-1-(benzo(b)thiophen-5yl)-2-[2(N,N-diethylamino)ethoxy]ethanol hydrochloride) is a novel compound which has been shown to exhibit a wide range of neurotrophic effects both in vivo and in vitro. This compound can slow the motor deterioration of wobbler mouse motor neuron disease. However, it is not known whether this compound has a trophic effect on spinal motor neurons. We have studied the effect of T-588 on neurite outgrowth and choline acetyltransferase(ChAT) activity in primary explant cultures of ventral spinal cord of fetal rats(VSCC). Cultures were treated with T-588 from day 1 to 1 week. T-588 treated VSCC, compared with control VSCC, had a significant neurite promoting effect at ranged between 10−8 molar(M) and 10−5 M, with 2.3 to 5.3 fold increased over that of control VSCC. In T-588 treated VSCC, ChAT activity was increased 1.5 times over that of control at 10−6, and 10−5 M respectively. Our data showing T-588 has neurotrophic action on VSCC and suggests a potential use of T-588 in treating diseases that involve degeneration and death of spinal motor neurons, such as motor neuropathy and motor neuron disease.

T-588 Protects Motor Neuron Death Following Axotomy

R(—)-1-(benzo [b] thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy] ethanol hydrochloride) (T-588) enhances acetylcholine release. This compound slows the motor deterioration of wobbler mouse motor neuron disease and enhances neurite outgrowth and choline acetyltransferase activity in cultured rat spinal motor neurons. We examined the ability of T-588 on axotomized spinal motor neuron death in the rat spinal cord. After the postnatal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of T-588 for 14 consecutive days rescued spinal motor neuron death. Our results showing in vivo neurotrophic activity of T-588 for motor neurons support the applicability of T-588 for the treatment of motor neuron diseases, such as amyotrophic lateral sclerosis and motor neuropathies.