Genjiro Hirose

Paramedian Pontine Infarction: Neurological/Topographical Correlation

BACKGROUND AND PURPOSE There have been few reports of pontine syndromes secondary to paramedian pontine infarctions. To clarify the clinicotopographical correlation and prognosis of paramedian pontine infarct syndromes, we analyzed the clinical signs and their association with MRI findings. METHODS We studied 49 patients with acute paramedian pontine infarcts and classified them into three subtypes on the basis of lesion location on MRI. Patient clinical status was assessed by Rankin Disability Scale (RDS) scores on admission and at 60 days after onset of stroke. RESULTS Twenty-seven patients had basal infarcts. Clinical findings included dysarthria (n = 27), hemiparesis with upper extremity predominance (n = 15), brachial monoparesis (n = 4), and pathological laughing (n = 3). Fifteen patients had basal-tegmental infarcts. Clinical findings presented with hemiparesis and horizontal gaze abnormalities, including abducens nerve palsy (n = 1), internuclear ophthalmoplegia (INO) (n = 5), horizontal gaze palsy (n = 1), one-and-a-half syndrome (n = 1), and superficial or proprioceptive sensory dysfunction (n = 8). Seven patients had tegmental infarcts. Clinical findings included INO (n = 1), horizontal gaze palsy (n = 2), one-and-a-half syndrome (n = 3), and sensory changes (n = 2). On both admission and 60 days later, the RDS scores of the patients with upper pontine lesions were significantly better than those with lower pontine lesions (P < .01). The RDS scores of the patients with basal-tegmental infarct in the upper pons were significantly better than those with infarct in the lower pons (P < .02). CONCLUSIONS Paramedian pontine infarcts, which are usually due to thrombosis of perforating arteries, presented with a faciobrachial dominant hemiparesis with dysarthria, somatosensory disturbance, and horizontal gaze abnormalities. The favorable outcome may be related to the level of the pontine lesion, which influences the effect on the corticospinal tract.

Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD

OBJECTIVE Cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinsons disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinsons Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. METHODS Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H-Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. RESULTS The early H/M ratio was significantly lower in patients with PD (1.45+/-0.207) than in the NCs (2.08+/-0.231), and in those with MSA (1.99+/-0.284), but not in those with DLB (1.29+/-0.0435). The delayed H/M ratio for PD (1.33+/-0.276) also was significantly decreased as compared to the ratios for NCs (2.17+/-0.286) and MSA (2.16+/-0.414) but not DLB (1.16+/-0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. CONCLUSION Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.

Non-N-methyl-d-aspartate glutamate receptors mediate oxygen–glucose deprivation-induced oligodendroglial injury

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.

Neuropathological studies of the spinal cord in early stage HTLV-I-associated myelopathy (HAM).

Necropsy findings for a patient with HTLV-I-associated myelopathy (HAM) of 9 months clinical duration are reported. Loss of myelin sheaths and axons together with perivascular lymphocytic infiltration was seen in the lateral and posterior columns of the spinal cord from the cervical to the lumbar region where vacuolar changes caused by the splitting of myelin sheaths were prominent. Immunohistochemical analyses revealed CD8+ cytotoxic T cell infiltration predominated in the absence of HTLV-I core protein antigen bearing-cells in the brain and spinal cord. Myelin sheath damage and predominant CD8+ cytotoxic T cell infiltration are thought to be the main neuropathological findings in the spinal cord in early stage HAM.

Cyclic AMP‐Elevating Agents Prevent Oligodendroglial Excitotoxicity

Abstract: Previously, we have demonstrated that cells of the oligodendroglial lineage express non‐NMDA glutamate receptor genes and are damaged by kainate‐induced Ca2+ influx via non‐NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte‐like cells, differentiated from the CG‐4 cell line established from rat oligodendrocyte type‐2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate‐induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8‐bromo‐cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3‐isobutyl‐1‐methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate‐induced cell death in an additive manner. A remarkable increase in Ca2+ influx (∼5.5‐fold) also was induced by kainate. The cyclic AMP‐elevating agents caused a partial suppression of the kainate‐induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate‐induced Ca2+ influx was partially reversed by H‐89, an inhibitor of cyclic AMP‐dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate‐induced Ca2+ influx. We therefore concluded that cyclic AMP‐elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP‐dependent protein kinase‐dependent protein phosphorylation, resulting in decreased kainate‐induced Ca2+ influx.

Mutation in the CHAC gene in a family of autosomal dominant chorea–acanthocytosis

Writ e Click is restricted to comments about studies published in Neurology ® within the past 8 weeks. The submission below represents an exception because it addresses a genetic sequencing error published in Neurology in 2003. In addition, these Writ e Click submissions will be available as open access to all readers in an effort to further publicize the Correction. In 2003, Saiki et al.1 reported an autosomal dominant transmission of chorea-acanthocytosis (ChAc) that constituted a significant challenge to the generally …

Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line.

Abstract: Previously, we have demonstrated that excitotoxicity of oligodendrocyte‐like cells (OLC), differentiated from immortalized rat O‐2A progenitor cells (CG‐4 cells), is prevented by cyclic AMP‐elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate‐induced injury was prevented by cyclic GMP analogues (8‐bromo‐cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3‐isobutyl‐1‐methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8‐bromo‐cyclic GMP were added, kainate‐induced injury was additively prevented. There was a strong positive correlation between suppression of kainate‐induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8‐bromo‐cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate‐induced Ca2+ influx was decreased by 8‐(4‐chlorophenylthiol)‐guanosine‐3′,5′‐monophosphate, an activator of cyclic GMP‐dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT‐PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG Iβ mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.

Binding of neuronal ELAV‐like proteins to the uridine‐rich sequence in the 3′‐untranslated region of tumor necrosis factor‐α messenger RNA

Tumor necrosis factor‐α (TNF‐α) is a proinflammatory cytokine that is involved in the pathogenesis of several human CNS disorders. The AU‐rich element (ARE) in the 3′‐untranslated region (UTR) of TNF‐α mRNA is implicated in post‐transcriptional control of TNF‐α. In this study, we showed that a human neuronal ELAV‐like protein binds to the ARE in the 3′‐UTR of TNF‐α mRNA. The protein binds to the uridine stretch in AUUUA pentanucleotides inside the ARE in the 3′‐UTR of TNF‐α mRNA. The TNF‐α mRNA‐binding region in the protein appears to be identical to the c‐myc and IL‐3 mRNA‐binding regions. Moreover, this study showed that in vitro treatment of neuroblastoma cells with interleukin‐4 (IL‐4), which inhibits TNF‐α production, reduced the expression of the neuronal ELAV‐like proteins. These results suggest that the expression of neuronal ELAV‐like proteins may be closely associated with the expression of TNF‐α in neuronal cells.

Chorea-acanthocytosis associated with Tourettism.

We report on a case of Chorea‐acanthocytosis (ChAc) in association with Tourettism that consisted of motor and vocal tics, attention deficit–hyperactivity disorder, and obsessive–compulsive disorder in addition to the typical symptoms of ChAc. The subject was compared with his elder sister who had the same disease but milder clinical profile and neuroradiological findings. The [18F]‐2‐fluoro‐2‐deoxyglucose positron emission tomography (FDG‐PET) findings did not explain the differences in symptomatology between the patient and his sister, although they may have correlated with severity.

A new method for estimation of nerve conduction velocity distribution in the frequency domain.

Nerve conduction velocity (NCV) measurements have been widely used to assess the electrophysiological properties of peripheral nerves and to detect neuropathies at a subclinical stage. Conventional NCVs are usually expressed as the NCV for the fastest conducting fibers and the current standard methods do neither supply information about slower conducting fibers, nor detect information about individual fiber groups. We present a new analytical method, to estimate the distribution of conduction velocity (DCV), based upon spectral analysis of the wave forms of two compound action potentials (CAPs) recorded by surface electrodes from a nerve bundle. If the spectra of the two CAPs recorded at two different sites in response to supramaximal electrical stimulation at distances l1 and l2 are given as G11(omega) and G12(omega), the spectral representation of the latency distribution P12(omega) for the propagation distance l2 is expressed as follows: P12(l1 omega/l2) = [G11(omega)/G12(omega)]P12(omega), where omega is an angular frequency. We developed an algorithm that computes P12(omega) successively without using iterative calculation methods. Our estimation method is theoretically based upon the principle that the CAPs are recorded monopolarly to estimate the DCV, but in practical use, it is almost impossible to obtain appropriate CAP wave forms by monopolar recording methods, because of stimulation and muscle artefacts. In order to evaluate the efficacy of bipolarly recorded CAP wave forms for this computation algorithm, we examined the two CAP wave forms reconstructed by simulation techniques. We found that the difference between the monopolar and bipolar recording methods was reflected in the wave form extracted for the single fiber action potentials but not in the latency distribution. The distance between the bipolarly recorded electrodes (1.5 cm was the minimal distance used) did not affect the reproducibility of estimating the latency distribution. This new method is non-invasive and could be used for evaluation of peripheral neuropathies.