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We report a 65-year-old man who was diagnosed with focal status epilepticus generating a dreamy state, delusions with anxiety, complex audiovisual hallucinations, elementary auditory hallucinations, and metamorphopsia with a growing large lateral temporal lobe lesion. After administrating anti-seizure drugs, all the symptoms disappeared, and brain magnetic resonance imaging revealed ipsilateral hippocampal sclerosis. To the best of our knowledge, this is the first report to present all the symptoms in one epilepsy case. On the basis of semiology, electroencephalography, and brain magnetic resonance imaging, we speculated that epileptic activities that have originated from the lateral lesion might have propagated to the ipsilateral mesial temporal lobe, causing hippocampal sclerosis.

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been associated with steroid-responsive cortical encephalitis and comorbid generalized epilepsy. A 44-year-old woman developed repeated epilepsia partialis continua (EPC) without generalized seizures and was anti-MOG antibody-positive. Radiological abnormalities were detected in the bilateral medial frontoparietal cortices, but there were no cerebrospinal fluid abnormalities. She achieved remission with anti-epileptic drugs alone. However, encephalitis recurred four months later when pleocytosis appeared, and steroid therapy was effective. Altogether, EPC without typical cerebrospinal fluid features can be an early sign of anti-MOG antibody-positive encephalitis. Thus, patients with EPC of unknown etiology need to be screened for anti-MOG antibodies.

We report on a 44-year-old woman who was diagnosed with toxic epidermal necrolysis (TEN) during the recovery phase from autoimmune limbic encephalitis with anti-glutamate receptor antibodies. Both, autoimmune limbic encephalitis and TEN are very rare diseases. The co-existence of the two diseases has not yet been reported. We speculate that the total of 18 drugs needed for the treatment of encephalitis might have increased the risk of TEN. Similar reports would be required to elucidate the pathophysiology of the co-existence.

This report describes a rare case presenting with dystonic seizures due to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. The patient was an 18-year-old woman with repeated right-dominant dystonic seizures even under sedation. Single-photon emission computed tomography (SPECT) showed intense hyperperfusion of the caudate nuclei, putamen, globus pallidus, thalamus, and insula on the left side, suggesting encephalitis. Antibodies against NMDA receptors were detected in the sera and cerebrospinal fluids. Immune-mediated treatments were administered. Three months later, the dystonic seizures disappeared. We diagnosed her with anti-NMDA receptor encephalitis. SPECT suggested that the main region of encephalitis was the basal ganglia. Therefore, we propose that the patient’s dystonic seizures may originate from the insula and be generated by intense hyperactivity of the basal ganglia.

Immune thrombocytopenic purpura (ITP) can increase the risk of not only hemorrhagic incidents but also thrombotic events. Although several patients with ITP who developed cerebral infarction have been reported, concurrence of spinal cord infarction and ITP has not been reported. We report the case of a female patient who developed spinal cord infarction during the exacerbation of her ITP. This case suggests a possible association between spinal cord infarction and ITP, which can cause paradoxical thrombosis.

The patient was a 64-year-old man who presented with gait disturbance at the age of 58. He was later diagnosed with Parkinson’s disease. At the age of 64, he felt severe right abdominal pain because his right abdomen was compressed by his abnormal posture. Neurological examinations showed axial flexion to the anterior and right sides, i.e. a combination of camptocormia and Pisa syndrome, and hypertrophy of the right lumbar paraspinal muscles in addition to parkinsonism. Surface electromyography and body computed tomography suggested axial dystonia, i.e. right dominant hyperactivity and hypertrophy of the lumbar paraspinal muscles. Botulinum toxin was injected into the right lumbar paraspinal muscles. One month later, his abnormal posture improved and his right abdominal pain was also relieved. In general, botulinum toxin treatment of the paraspinal muscles has the potential to improve Pisa syndrome but carries the risk of worsening camptocormia. However, in our case, not only Pisa syndrome but also camptocormia improved. Therefore, we should note that botulinum toxin treatment of paraspinal muscles is able to improve not only Pisa syndrome but also camptocormia. As a plausible explanation, botulinum toxin treatment could control the hyperactivity of the bilateral paraspinal muscles symmetrically, which might improve camptocormia in addition to Pisa syndrome.

We investigated the relationship between the involvement of the cauda equina in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the increment of cerebrospinal fluid (CSF) protein. We measured cauda equina conduction time (CECT) in 14 CIDP patients using magnetic stimulation with a MATS coil. Statistical analysis revealed that CECT and CSF protein had a significant positive linear correlation. Conduction time of the peripheral nerve trunk, in contrast, had no significant linear correlation with CSF protein. We revealed that the involvement of the cauda equina and increment of CSF protein are closely related. In CIDP cases with elevated CSF protein, spinal nerves including the cauda equina are very likely involved.

Objective: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti–transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. Methods: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[−] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Results: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(−) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(−) and exhibited no dC5b-9 or VFs. Conclusions: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(−) CAM.

The proximal segment of peripheral nerves is assumed to be involved in both demyelinating and axonal types of Guillain-Barré syndrome (GBS). However, electrophysiological examinations have not yet clarified if this segment is involved. We measured cauda equina conduction time (CECT) in nine demyelinating GBS and seven axonal GBS patients. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis muscle. Electrical stimulation was given at the ankle and the knee, and magnetic stimulation was given over the first sacral (S1) and first lumbar (L1) spinous processes using a magnetic augmented translumbosacral stimulation (MATS) coil. CECT was obtained by subtracting S1-level latency from L1-level latency. CECT was prolonged in all the patients with demyelinating GBS who had leg symptoms, whereas motor conduction velocity (MCV) at the peripheral nerve trunk was normal in all the patients. In all the patients with axonal GBS having leg symptoms, CECT and MCV were normal and no conduction blocks were detected between the ankle and the neuro-foramina. The cauda equina is much more frequently involved than the peripheral nerve trunk in demyelinating GBS. In axonal GBS, usually, CECT is normal and segmental lesions are absent between the ankle and the neuro-foramina. Therefore, the CECT measurement should be very useful for directly detecting demyelinating lesions in GBS.

We describe the case of a 34-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. She developed transient ischemic attack after the introduction of lenalidomide plus dexamethasone (Rd) therapy despite no vascular risk factors. Magnetic resonance and computed tomography angiographies showed bilateral internal carotid artery stenosis. Rd therapy was suspended because of its thromboembolic risk. She had been neurologically stable during the suspension of Rd therapy. After Rd therapy was restarted, however, she repeated ischemic cerebrovascular disease. Rd therapy was switched to carfilzomib plus dexamethasone therapy. Thereafter, she had been neurologically stable. Multivessel stenosis is infrequently seen in POEMS syndrome. Therefore, magnetic resonance angiography should be performed before introducing Rd therapy in POEMS syndrome.

Neuroferritinopathy is a hereditary neurodegenerative disorder caused by mutations in the ferritin light chain gene (FTL1). The cardinal features are progressive movement disturbance, hypoferritinemia, and iron deposition in the brain. To date, five mutations have been described in Caucasian and Japanese families, but the genotype-phenotype correlations remain to be established. We identified a novel FTL1 mutation (exon 4, c.641/642, 4-nucletotide duplication) in a Japanese family and compared the clinical traits with those previously reported. All mutations but one are insertions in exon 4, resulting in frameshifts. Clinical features are similar among patients with the same mutations. Middle-age onset chorea is common in patients with insertions in the 5' portion of exon 4 including our cases, whereas patients with insertions in the 3' portion of exon 4 develop early-onset tremor, suggesting genotype-phenotype correlations. In this family, male predominance and normal serum ferritin levels are characteristic.

The present report describes the case of a 57-year-old male patient with spinal dural arteriovenous fistula (AVF). During the diagnostic examination, intravenous steroid therapy was implemented. The next day, the patient's symptoms were mildly improved and magnetic resonance imaging showed that the spinal cord swelling was markedly reduced. After the angiographic diagnosis of spinal dural AVF fed from the radicular artery originating from the sixth intercostal artery, the shunts were surgically interrupted by cutting the drainage vein. Clinical deterioration after steroid therapy was reported in several previous papers on this disorder. Based on the present case, however, we propose the possibility that intravenous steroid therapy is a viable option for presurgical management.

AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT–PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS.

Objective The long-term use of levodopa to treat Parkinson's disease (PD) is often limited by the development of motor complications (e.g., levodopa-induced dyskinesia, LID). We hypothesized that a non-ergot dopamine agonist with strong affinity for D3) dopamine receptors (pramipexole) may improve LID in patients taking an ergot D1/D2 dopamine agonist. Methods Patients with PD and LID being treated with levodopa in addition to an ergot dopamine agonist were randomized to either a group in which pramipexole was added to current medications or a group in which the ergot dopamine agonist was switched to pramipexole. Dyskinesia was evaluated using Core Assessment Program for Surgical Interventional Therapies scores. The unified Parkinson's disease rating scale scores, modified Hoehn and Yahr stages (at 'on' time), Parkinson's disease questionnaire-39 scores and clinical global impression-improvement scores were also used for evaluation. Results At 24 weeks, pramipexole alleviated LID with more efficiency in the switch group. Conclusion Pramipexole may be a therapeutic option for treating LID because its effects on D3 dopamine receptors may balance the D1 dopamine receptor supersensitivity associated with LID.

Dentatorubral–pallidoluysian atrophy (DRPLA) is associated with the expansion of an unstable GAG repeat. Using antibodies against a synthetic peptide corresponding to the sequence of the DRPLA gene product C terminus, we have identified the DRPLA gene product in normal human brains as a ≈190 kD protein. We also find a larger ≈205 kD protein specifically in DRPLA brains. Immunohistochemically, the DRPLA gene product is observed mainly in the neuronal cytoplasm. Our results demonstrate the existence of the expanded GAG repeat gene product and support the possibility that the expanded CAG–encoded polyglutamine stretch may participate in the pathological process of the similar trinucleotide repeat diseases.

This report describes a rare case of hypertrophic pachymeningitis secondary to antiphospholipid syndrome in a 37-year-old woman. The patient had a history of antiphospholipid syndrome and developed hypertrophic pachymeningitis subsequently. Pathological examination of the dura mater showed not only fibrous thickening, the typical finding of hypertrophic pachymeningitis, but also thrombosis in the dural microvessels and T cell infiltration without B cell or plasma cell infiltration, suggesting cell-mediated immunity. The dural thickening spontaneously improved and did not deteriorate during corticosteroid therapy. The histological findings and spontaneous remission observed in this case might be characteristic of secondary hypertrophic pachymeningitis with antiphospholipid syndrome. Further investigations are necessary to elucidate the pathophysiology of this novel type of hypertrophic pachymeningitis.

This report describes a rare case presenting with focal epilepsy and focal dystonia associated with glutamate receptor δ2 antibody. The patient was a 47-year-old male patient with neurosyphilis. He presented with an intractable focal seizure spreading from the right arm, with dystonia of the left leg. The IgG antibody of glutamate receptor δ2 was detected. Ictal and interictal SPECT suggested focal epilepsy in the left frontal cortex. Antibiotic and antiepileptic drugs were ineffective, although steroid pulse therapy effectively diminished the patient's symptoms. Inflammatory mechanisms may have contributed to this disorder.

This report describes the case of a 71-year-old woman with a limited form of neuromyelitis optica (NMO) who had a longitudinally extensive spinal cord lesion from the fourth to the tenth thoracic vertebrae. Up to age 75, she had four subsequent recurrences of the myelitis within the same spinal cord area but with no optic neuritis. Anti-AQP4 antibody was seropositive. Recurrence within the same spinal cord area might be a characteristic clinical finding in NMO spectrum disorders. For such patients, examination for anti-AQP4 antibody might be necessary for the diagnosis and therapy of this disorder.

Background: Interferon-β-1b (IFNβ-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNβ-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNβ-1b to identify similar cases. Methods: At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNβ-1b therapy. Results: Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale ≧7.0) within 90 days of the initiation of IFNβ-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNβ-1b therapy were more severe than those experienced by the individual patients before the use of IFNβ-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFβ-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. Conclusions: Our study suggests that IFNβ-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFβ-1b therapy, cases in NMO spectrum should be carefully excluded.

Recently, a cardiac disorder characterized by ballooning and hypokinesis at the apex has been described as takotsubo (ampulla-shaped) cardiomyopathy. We encountered a patient with a rare case of takotsubo cardiomyopathy associated with microscopic polyangiitis. A 70-year-old woman suddenly presented with ventricular dysfunction during the active phase of microscopic polyangiitis. The findings on echocardiograms and electrocardiograms were consistent with those of takotsubo cardiomyopathy. The ventricular dysfunction completely resolved after treatment with 40 mg/day of prednisolone and methylprednisolone pulse therapy. This unique type of cardiomyopathy can be a complication of microscopic polyangiitis.

Somatic mosaicism of an expanded repeat is present in tissues of patients with triplet repeat diseases. Of the spinocerebellar ataxias associated with triplet repeat expansion, the most prominent heterogeneity of the expanded repeat is seen in dentatorubral-pallidoluysian atrophy (DRPLA). The common feature of this somatic mosaicism is the difference in the repeat numbers found in the cerebellum as compared to other tissues. The expanded allele in the cerebellum shows a smaller degree of expansion. We previously showed by microdissection analysis that the expanded allele in the granular layer in DRPLA cerebellum has less expansion than expanded alleles in the molecular layer and white matter. Whether this feature of lesser expansion in granule cells is common to other types of neurons is yet to be clarified. We used a newly developed excimer laser microdissection system to analyze somatic mosaicism in the brains of two patients, one with early- and another with late-onset DRPLA, and used single cell PCR to observe the cell-to-cell differences in repeat numbers. In the late onset patient, repeat expansion was more prominent in Purkinje cells than in granule cells, but less than that in the glial cells. In the early onset patient, repeat expansion in Purkinje cells was greater than in granule cells but did not differ from that in glial cells. These findings suggest that there is a difference in repeat expansion among neuronal subgroups and that the number of cell division cycles is not the only determinant of somatic mosaicism.

Huntington's disease (HD) is a neurodegenerative disorder characterized by the expansion of CAG repeats in exon 1 of the HD gene. To clarify the instability of expanded CAG repeats in HD patients, an HD model mouse has been generated by gene replacement with human exon 1 of the HD gene with expansion to 77 CAG repeats. Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues. One or two CAG repeat expansion was found in litters from paternal transmission, whereas contraction of CAG repeat in litters was observed through maternal transmission. Elderly mice show greater CAG repeat instability than younger mice, and a unique case was observed of an expanded 97 CAG repeat mouse. Somatic CAG repeat instability is particularly pronounced in the liver, kidney, stomach, and brain but not in the cerebellum of 100-week-old mice. The same results of expanded CAG repeat instability as observed in this HD model mouse were confirmed in the human brain of HD patients. Glial fibrillary acidic protein (GFAP)-positive cells have been found to be increased in the substantia nigra (SN), globus pallidus (GP), and striatum (St) in the brains of 40-week-old affected mice, although without neuronal cell death. The CAG repeat instability and increase in GFAP-positive cells in this mouse model appear to mirror the abnormalities in HD patients. The HD model mouse may therefore have advantages for investigations of molecular mechanisms underlying instability of CAG repeats. J. Neurosci. Res. 65:289–297, 2001. © 2001 Wiley-Liss, Inc.

Three autosomal dominant spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), and spinocerebellar ataxia type 1 (SCA1), are associated with the expansion of a CAG repeat in the respective genes. To investigate the association between CAG repeat expansion and neuropathological findings, we analyzed several brain regions from 9 cases of DRPLA, 3 cases of MJD, and 1 case of SCA1. We found that the expanded alleles were smaller in the cerebellar cortex than in other brain regions, such as the frontal cortex, in these three diseases. The discrepancy in the expanded CAG repeat length between cerebellar cortex and other tissues was most prominent in DRPLA, and especially in cases of adult-onset DRPLA. A significant correlation was found between the age at onset of DRPLA and the size of the CAG repeat expansion. Cerebella of DRPLA patients were microscopically dissected into three layers, the molecular and granular layers and the white matter, which were analyzed separately. The lower level of CAG repeat expansion in DRPLA cerebella was representative of CAG repeat expansion in the granule cells. The microdissected samples of the granular layer of the hippocampal formation, which is densely packed with neuronal cells, revealed that the degree of CAG repeat expansion in this layer was similar to that in the cerebellum. These observations suggest that granule cells in the cerebellum and hippocampus have low levels of CAG repeat expansion, and that other types of cells exhibit a higher level of CAG repeat expansion, in spinocerebellar ataxias.

Machado-Joseph disease (MJD) is an autosomal dominant disorder characterized pathologically by spinocerebellar degeneration. Recently, an expansion of CAG repeat in a gene located at the chromosome 14q32.1 was found to be responsible for the disease. Here, we investigated in situ the expression of the MJD gene (MJD1) in the central nervous systems of normal and affected individuals and in rat brains. This gene was expressed in all regions of rat and human normal brains with certain regional variations. MJD1 was transcribed preferentially in neurons, although low levels of MJD1 mRNA were also observed in glial cells. Neurons susceptible to degeneration in MJD expressed MJD1 but not selectively. In the affected brains, the MJD1 mRNA distribution and amount in all the areas examined were similar in patients and controls. In addition, the cellular MJD1 mRNA level correlated neither with clinical severity nor expanded length. Our study showed that the expression levels of trinucleotide repeats in MJD patients and normal controls did not differ, indicating that the pathogenesis of MJD may involve direct toxicity to vulnerable subsets and/or region-specific cofactors of MJD proteins.

We report a patient with primary progressive aphasia who first presented with amnesic aphasia that developed over the course of 3 years into nonfluent aphasia with buccofacial apraxia, followed in the next year by cognitive impairment and parkinsonism. Pathological findings were typical for corticobasal degeneration except for the distribution of cortical atrophy. This case suggests that corticobasal degeneration should be included in the differential diagnosis of primary progressive aphasia, especially in association with parkinsonism.