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ABSTRACT: Atrophy of the pontine tegmentum and facial colliculus is a characteristic pathological feature of Machado-Joseph disease. We assessed whether this finding can be detected by conventional brain magnetic resonance imaging. A total of 17 patients with genetically confirmed Machado-Joseph disease, 15 disease controls (spinocerebellar ataxia type 6 and dentatorubral-pallidoluysian atrophy), and 17 normal subjects were examined using a 1.5-Tesla magnetic resonance imaging scanner. The widths of the facial colliculus, pontine tegmentum, and pontine base and the area of the fourth ventricle were measured on axial T2-weighted imaging. Pathological examination was performed in 9 Machado-Joseph disease patients. In addition, visual inspection of the facial colliculus was evaluated by receiver operating characteristic analysis. The width of the facial colliculus was significantly smaller in Machado-Joseph disease patients (0.37 ± 0.16 mm; mean ± standard deviation) than in normal subjects (0.73 ± 0.30 mm; P < .01), whereas the width of the pontine tegmentum was smaller in both Machado-Joseph disease (4.85 ± 0.58 mm) and dentatorubral-pallidoluysian atrophy (4.72 ± 0.59) patients than in normal subjects (6.35 ± 0.74 mm; P < .01). Visual evaluation of the facial colliculus showed sufficient area under the receiver operating characteristic curves to differentiate Machado-Joseph disease from dentatorubral-pallidoluysian atrophy (0.78) and spinocerebellar ataxia type 6 (0.87). Pathological evaluation showed significant atrophy of the facial colliculus in all Machado-Joseph disease patients. Atrophy of the facial colliculus is a feasible magnetic resonance imaging finding for diagnosing Machado-Joseph disease, and it is easily found as a flattening of the fourth ventricular floor.
Movement Disorders 06/2012; 27(8):1041-6. · 4.51 Impact Factor
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ABSTRACT: Intravascular lymphoma (IVL) is a rare disease form of malignant lymphoma, and it is characterised by the selective growth of lymphoma cells within the lumina of vessels. Identification of this disease at an early stage is difficult because of non-specific clinical symptoms and neuroradiological findings. Most reported IVL cases are diagnosed at post-mortem following autopsy. We report the case of a patient who presented with status epilepticus (SE) as the initial manifestation of IVL. Despite the administration of anti-convulsant agents and general care the patient's condition deteriorated rapidly after admission, culminating in death due to respiratory failure and heart failure 21 days after the onset of symptoms. Post-mortem examination revealed IVL in the brain and multiple organs. Epileptic seizures often appear during the clinical course of IVL; however, they occur most frequently at advanced stages. Diagnosis of IVL that first presents with SE is of clinical importance because the treatment and prognosis of acute SE arising from IVL are different from those of SE originating from other causes.
Case Reports in Neurology 01/2012; 4(2):107-12.
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Kazumoto Shibuya,
Sonoko Misawa, Kimihito Arai,
Miho Nakata,
Kazuaki Kanai,
Yasumasa Yoshiyama,
Kimiko Ito,
Sagiri Isose,
Yu-ichi Noto,
Saiko Nasu,
Yukari Sekiguchi,
Yumi Fujimaki,
Shigeki Ohmori,
Hiroshi Kitamura,
Yasunori Sato,
Satoshi Kuwabara
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ABSTRACT: Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To clarify changes in axonal ion channel expression in motor axons of ALS, we performed immunohistochemistry of potassium and sodium channels in the C7 and L5 ventral/dorsal roots obtained from five autopsy cases of sporadic ALS. Compared to controls, the immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the ALS patients. Nodal sodium channel expression was not significantly different in ALS patients and control subjects. Our results show prominently reduced expression of axonal potassium channels, and provide the neuropathological and biological basis for decreased accommodative potassium currents in motor axons of ALS patients. The axonal hyperexcitability would lead to generation of fasciculations, and possibly enhances motor neuron death in ALS.
Experimental Neurology 08/2011; 232(2):149-53. · 4.70 Impact Factor
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ABSTRACT: Anticholinergics, and drugs with anticholinergic properties, are widely and frequently prescribed, especially to the elderly. It is well known that these drugs decrease cognitive function and increase the risk of dementia. Although the mechanism of anticholinergic drug-induced cognitive impairment has been assumed to be functionally reduced acetylcholine (ACh) neurotransmission, some data have indicated that anticholinergics might enhance the pathology of Alzheimer's disease. In this study, we investigated the pathological effects of anticholinergics on neurodegeneration. We chronically administered two anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less central anticholinergic action), to neurodegenerative tauopathy model mice 2 to 10 months old. Furthermore, because the ACh nervous system regulates both central and peripheral inflammation, we administered TP or PP to PS19 mice in which we had artificially induced inflammation by lipopolysaccharide injection. Tau pathology, synaptic loss, and neurodegeneration in the hippocampal region, as well as tau insolubility and phosphorylation, were markedly increased in TP-treated mice and mildly increased in PP-treated mice. Furthermore, immunohistochemical analysis revealed microglial proliferation and activation. Moreover, anticholinergics increased interleukin-1β expression in both the spleen and brain of the tauopathy model mice intraperitoneally injected with lipopolysaccharide to induce systemic inflammation. Interestingly, these alterations were more strongly observed in TP-treated mice than in PP-treated mice, consistent with the level of central anticholinergic action. Anticholinergic drugs not only impair cognitive function by decreased ACh neurotransmission, but also accelerate neurodegeneration by suppressing an ACh-dependent anti-inflammatory system. Anticholinergics should be less readily prescribed to reduce the risk of dementia.
Neurobiology of Disease 08/2011; 45(1):329-36. · 5.40 Impact Factor
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ABSTRACT: Neuromyelitis optica (NMO) is assumed to be immunologically distinct from multiple sclerosis (MS). Adequate studies about cytokines and chemokines in NMO have been lacking.
To investigate the contribution of cytokines/chemokines in the pathogenesis of NMO.
We measured 27 cytokines/chemokines and Th17 cell-associated cytokines in the cerebrospinal fluid (CSF) of 31 NMO, 29 MS and 18 other non-inflammatory neurological disorders patients. The serum levels of some cytokines/ chemokines were also measured. The correlations between clinical characteristics/laboratory findings and levels of cytokines/chemokines in NMO were examined.
The CSF levels of interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-13 and granulocyte colony-stimulating factor were significantly increased in NMO, while IL-9, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein-1-beta and tumor necrosis factor-alpha were increased in MS. IL-10 and interferon-gamma-inducible protein-10 were elevated in NMO and MS. In serum analyses, only the IL-6 level showed significant elevation in NMO. The CSF IL-6 level had a significant correlation with the CSF glial fibrillary acidic protein level and CSF cells, and a weak correlation with anti-aquaporin-4 antibody titers.
Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO.
Multiple Sclerosis 12/2010; 16(12):1443-52. · 4.26 Impact Factor
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Clinical neurology and neurosurgery 10/2010; 113(2):139-41. · 1.30 Impact Factor
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ABSTRACT: Acetylcholinesterase inhibitors (AChEIs) are widely used to compensate for acetylcholine (ACh) depletion in the Alzheimer's disease (AD) brain. Some clinical and experimental studies, however, have suggested that AChEIs also provide neuroprotection. To assess the effect of AChEIs on neurodegeneration, donepezil (DZ), an AChEI, was administered to FTDP-17 model mice with a P301S tau mutation (line PS19). Eight months of DZ treatment resulted in amelioration of neuroinflammation, tau pathology, synaptic loss, and neuronal loss, as well as decreased tau insolubility and phosphorylation. Tau kinase activity analysis demonstrated significantly suppressed c-Jun N-terminal kinase (JNK) in the brains of DZ-treated PS19 mice. Recently, ACh has been shown to suppress inflammation, which plays a role in neurodegeneration. To confirm the anti-inflammatory effect of DZ, PS19 mice were injected with lipopolysaccharide, in combination with or without DZ, for one month. Results demonstrated that DZ suppressed IL-1β and COX-2 expression in the brain, as well as the spleen, suggesting that DZ directly prevents systemic inflammation. These data indicated that ACh did not act just as a cognition-linking neurotransmitter, but might suppress pathological mechanisms of neurodegeneration via anti-inflammatory action.
Journal of Alzheimer's disease: JAD 01/2010; 22(1):295-306. · 3.74 Impact Factor
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ABSTRACT: Two patients with a condition clinically resembling juvenile muscular atrophy of distal upper extremity (Hirayama disease) showed forward protrusive movement of the posterior cervical dura matter during neck flexion. The dura displacement was characteristically limited in an approximately central portion of the posterior dura, which is different from Hirayama disease, which exhibits whole posterior dura displacement. Interestingly, the restricted dura in these patients showed thickening with reduced elastic fibers, indicating that the decreased stretchability of the posterior dura had caused motor dominant cervical myelopathy.
Journal of Neurology 12/2009; 257(1):149-51. · 3.47 Impact Factor
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Kazuaki Kanai,
Masato Asahina, Kimihito Arai,
Hiroyuki Tomiyama,
Yoichi Kuwabara,
Tomoyuki Uchiyama,
Yukari Sekiguchi,
Manabu Funayama,
Satoshi Kuwabara,
Nobutaka Hattori,
Takamichi Hattori
Movement Disorders 06/2009; 24(9):1403-4. · 4.51 Impact Factor
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ABSTRACT: To assess heart rate (HR) regulation in Machado-Joseph disease (MJD), we evaluated HR variability at rest and the initial HR response to standing suddenly in 13 MJD patients and 26 normal control subjects. A head-up tilt (HUT) test involving the monitoring of blood pressure, HR, and cerebral oxy/deoxyhemoglobin concentration was also performed in each participant. There was no significant difference in HR variability at rest between the two groups, but the transient HR rise just after standing suddenly in the MJD group was significantly less than that in the control group (p < 0.01). The HUT test, where each participant was gradually tilted upward, induced a significantly greater HR increase in the MJD group compared with the controls (p < 0.01), while there were no significant differences in the blood pressure and cerebral oxygenation changes between the two groups. In our MJD study, the transient HR rise just after standing suddenly was diminished, and HR markedly increased during sustained orthostatic stress.
The Cerebellum 12/2008; 8(2):130-6. · 3.21 Impact Factor
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ABSTRACT: Tufted astrocytes (TAs) are considered reliable, specific markers for the neuropathologic diagnosis of progressive supranuclear palsy (PSP). It is known that neurofibrillary tangles (NFTs) may relate directly to neurodegeneration, but the role of glial tau pathology is not well determined. To examine the hypothesis that TAs are as pathogenic as NFTs and that both might have a common accumulation, we evaluated the topographic relationship between TAs and NFTs in 12 cases of PSP. The sections of 13 different parts of the brain were stained using the Gallyas-Braak method, and TAs and NFTs were counted and compared statistically. The number of TAs significantly correlated with that of NFTs in the central gray matter, pontine nuclei, and tegmentum, which are responsible for the main symptoms in PSP. In the examined allocortex, however, NFTs were abundant without accompanying TAs. Staining with the specific antibody for 4-repeat tau (RD4) and 3-repeat tau (RD3) was performed to clarify this discrepancy from the standpoint of tau isoforms. NFTs in the entorhinal cortex were stained with both RD3 and RD4, but NFTs in the premotor cortex were stained with only RD4. The nature of NFTs in the allocortical area was different from that of the isocortex in PSP. TAs in the isocortex may share the same pathologic cascade with NFTs stained only by RD4. These results suggest that TAs are part of the same pathologic process as NFTs in PSP.
Acta Neuropathologica 07/2008; 115(6):623-8. · 9.32 Impact Factor
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Shigeki Hirano,
Hitoshi Shinotoh, Kimihito Arai,
Akiyo Aotsuka,
Fumihiko Yasuno,
Noriko Tanaka,
Tsuneyoshi Ota,
Koichi Sato,
Kiyoshi Fukushi,
Shuji Tanada,
Takamichi Hattori,
Toshiaki Irie
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ABSTRACT: To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.
Movement Disorders 07/2008; 23(8):1154-60. · 4.51 Impact Factor
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Shigeki Hirano MD,
PhD Hitoshi Shinotoh MD,
Kimihito Arai MD,
PhD Akiyo Aotsuka MD,
PhD Fumihiko Yasuno MD,
PhD Noriko Tanaka MD,
PhD Tsuneyoshi Ota MD,
PhD Koichi Sato MD,
Kiyoshi Fukushi PhD,
PhD Shuji Tanada MD, [......], Kimihito Arai,
Akiyo Aotsuka,
Fumihiko Yasuno,
Noriko Tanaka,
Tsuneyoshi Ota,
Koichi Sato,
Kiyoshi Fukushi,
Shuji Tanada,
Takamichi Hattori,
Toshiaki Irie
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ABSTRACT: To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [11C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (−27%) and the posterior lobe of cerebellar cortex (−36%) in patients with MSA-C and in the thalamus (−23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders. © 2008 Movement Disorder Society
Movement Disorders 06/2008; 23(8):1154 - 1160. · 4.51 Impact Factor
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Kazuaki Kanai,
Ryuji Sakakibara,
Tomoyuki Uchiyama,
Zhi Liu,
Tatsuya Yamamoto,
Takashi Ito,
Shigeki Hirano,
Masato Asahina,
Satoshi Kuwabara,
Takamichi Hattori,
Goro Fukami, Kimihito Arai,
Chiharu Yamaguchi,
Fumio Nomura
Movement Disorders 03/2007; 22(3):441-3. · 4.51 Impact Factor
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ABSTRACT: In injured adult neurons, the process of axonal regrowth and reestablishment of the neuronal function have to be activated. We assessed in this study whether RhoA, a key regulator of neurite elongation, is activated after injury to the peripheral nervous system. RhoA is activated in motoneurons but not in Schwann cells after mouse sciatic nerve injury. To examine whether the activation of RhoA and its effector, Rho-kinase, retards axon regeneration of injured motoneurons, we employed a Rho-kinase inhibitor, fasudil. Amplitudes of distally evoked compound muscle action potentials are increased significantly faster after axonal injury in mice treated with fasudil compared with controls. Histological analysis shows that fasudil treatment increases the number of regenerating axons with large diameter, suggesting that axon maturation is facilitated by Rho-kinase inhibition. In addition, fasudil does not suppress the myelination of regenerating axons. These findings suggest that RhoA/Rho-kinase may be a practical molecular target to enhance axonal regeneration in human peripheral neuropathies.
Journal of the Peripheral Nervous System 10/2006; 11(3):217-24. · 2.80 Impact Factor
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Takashi Ito,
Ryuji Sakakibara,
Tatsuya Yamamoto,
Tomoyuki Uchiyama,
Zhi Liu,
Masato Asahina,
Morihiro Higashi, Kimihito Arai,
Shoichi Ito,
Yusuke Awa,
Kaori Yamamoto,
Mika Kinou,
Tomonori Yamanishi,
Takamichi Hattori
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ABSTRACT: Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves.
Clinical Autonomic Research 03/2006; 16(1):66-71. · 1.30 Impact Factor
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ABSTRACT: Cortical dysplasia has been increasingly recognized as a cause of epilepsy. We describe herein a 31-year-old female patient with epilepsia partialis continua (EPC) in the right extremities, which had lasted for 15 years without generalized seizures and other neurological deteriorations. MRI showed a focal thickening around the left motor area, indicative of cortical dysplasia, with adjacent subcortical abnormal T2 high intensity, suggestive of dysmyelination. Transcranial magnetic stimulation revealed low motor thresholds and markedly prolonged latencies of motor-evoked potentials (MEP) of the affected side, consistent with hyperexcitability of the cortical motoneurons accompanied by dysmyelination. This case demonstrates that motor cortex dysplasia can result in a mild and non-progressive form of epilepsia partialis continua, associated with the characteristic MRI and MEP abnormalities.
Journal of the Neurological Sciences 11/2004; 225(1-2):157-60. · 2.35 Impact Factor
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Parkinsonism & Related Disorders 07/2004; 10(4):255-6. · 3.80 Impact Factor
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ABSTRACT: Machado-Joseph disease (MJD), or hereditary spinocerebellar ataxia type 3, is the most common dominantly inherited ataxia. However, lower urinary tract (LUT) dysfunction in MJD has not been fully delineated. We investigated LUT dysfunction in MJD by clinical-urodynamic observations.
In 24 genetically diagnosed MJD, we recruited all 11 patients with LUT symptoms (six men, five women; age, 18-61 [mean 48] years; disease duration, 2-24 [mean 9] years; voiding difficulty, 7, urinary incontinence, 4). Urodynamic studies consisted of uroflowmetry, measurement of post-void residuals and electromyography (EMG)-cystometry. Neurophysiology tests consisted of motor unit potential (MUP) analysis of the sphincter and extremity muscles, tibial nerve somatosensory evoked potentials (SEP) and nerve conduction studies (NCS) of the extremities.
Urodynamic abnormalities were seen in all 11 patients studied. Maximum or average flow rate was decreased in five. Post-void residual was noted in three but residual urine volume > 100 ml was noted in only one patient. Maximum urethral closure pressure was low in one and high in one of five patients studied. EMG-cystometry during filling showed detrusor overactivity in five, impaired bladder sensation in four, low compliance detrusor in one, uninhibited sphincter relaxation in one and incompetent urethra in one. Voiding phase abnormalities included detrusor areflexia in three and detrusor-sphincter dyssynergia in two. Bethanechol supersensitivity of the bladder was noted in one of three patients studied. Bulbocavernosus reflex was absent in two of five patients studied. MUP analysis showed neurogenic changes in six of nine sphincter muscles and in all six extremity muscles studied. Five patients had prolonged or absent cortical response in SEP and four had sensory axonal neuropathy in NCS, which were relevant to the impaired bladder sensation.
In the present study, a half of MJD patients had LUT symptoms and they showed various urodynamic abnormalities. Detrusor overactivity, impaired bladder sensation, and neurogenic sphincter EMG were common findings, and large post-void residuals were rare. These findings are relevant to central and peripheral nervous system pathology of MJD.
Journal of the Neurological Sciences 03/2004; 218(1-2):67-72. · 2.35 Impact Factor
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ABSTRACT: We report a young, mentally retarded apprentice cook with a 2-month history of right upper extremity dystonia, for whom diazepam therapy was efficacious. We evaluated brain perfusion by single photon emission tomography (SPECT) before and after diazepam treatment. The abnormal hyperperfusion in the left thalamus and hypoperfusion in the left frontal cortex were normalized on the second SPECT under the successful diazepam treatment. These findings were indicative of functional changes in the left thalamus and left frontal cortex.
Parkinsonism & Related Disorders 07/2003; 9(5):253-6. · 3.80 Impact Factor
