Tomohiko Nakamura

Nagoya University, Nagoya, Aichi, Japan

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Publications (40)126.31 Total impact

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    ABSTRACT: Cardiac meta-iodobenzylguanidine (MIBG) uptake on 123I-MIBG cardiac scintigraphy is reduced in patients with Lewy body disease such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure, and has been reported to be useful for differentiating PD from other parkinsonian syndromes, as well as DLB from Alzheimer disease (AD). Postmortem studies have shown that the number of tyrosine hydroxylase (TH)-immunoreactive nerve fibers of the heart was decreased in pathologically-confirmed Lewy body disease, supporting the findings of reduced cardiac MIBG uptake in Lewy body diseases. Now, reduced cardiac MIBG uptake can be a potential biomarker for the presence of Lewy bodies in the nervous system. 123I-MIBG cardiac scintigraphy can allow us to determine the presence of Lewy bodies.
    No preview · Article · Feb 2016 · Ageing research reviews
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    ABSTRACT: We describe the case of a 33-year-old man with a 4-year history of worsening muscle stiffness and weakness in his right hand. He showed elevated serum creatine kinase levels at the onset of muscle stiffness that was characterized by delayed muscle relaxation after voluntary contraction. This symptom often occurred during cold exposure, and was partially attenuated by sodium channel blockade. Electrodiagnostic findings in repetitive nerve stimulation, short-exercise, and cooling tests were normal. Electromyography showed chronic denervation potentials in his cranial, cervical, thoracic, and lumbosacral myotomes without myotonic discharge. He exhibited facial and tongue fasciculations, hypernasality, gynecomastia, neurogenic changes in muscle biopsy, and increased serum testosterone levels. Spinal and bulbar muscular atrophy (SBMA) was diagnosed on the basis of the CAG trinucleotide expansion in the gene coding androgen receptor. A myotonia-like symptom without myotonic discharge may present as an early neurological sign of SBMA, which possibly reflects a sodium channel dysfunction in skeletal muscles.
    No preview · Article · Sep 2015 · Neuromuscular Disorders
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    ABSTRACT: Most patients with multiple system atrophy (MSA) develop autonomic dysfunction; however, orthostatic hypotension is not always present. Failure of the vasoconstrictor response is thought to be responsible for orthostatic hypotension, but the degree of impairment of this response in patients with MSA is unclear. We assessed autonomic function in patients with MSA by evaluating the vasoconstrictive response during a head-up tilt test and determining its relationship to orthostatic hypotension. As an additional examination, the efficacy of norepinephrine in treating orthostatic hypotension was also assessed. The study included 82 patients with MSA and 28 controls. Measures of total peripheral resistance were obtained during a head-up tilt test. Norepinephrine was administered to the patients lacking a vasoconstrictive response to evaluate its ability to treat orthostatic hypotension. At a 60° tilt, orthostatic hypotension occurred in 47.6% of the patients and 0% of controls. Reduction in total peripheral resistance from baseline at a 60° tilt was observed in 69.5% of the patients and 0% of controls. In patients with MSA, changes in systolic blood pressure from the baseline at a 60° tilt correlated positively with changes in the total peripheral resistance (r = 0.69, p < 0.0001). Norepinephrine prevented the reduction of total peripheral resistance and development of orthostatic hypotension. A large number of patients with MSA with and without orthostatic hypotension have an impaired peripheral vasoconstrictive response, suggesting a high frequency of cardiovascular dysautonomia with an associated risk of developing orthostatic hypotension. A norepinephrine infusion was effective for treating orthostatic hypotension. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · May 2015 · Parkinsonism & Related Disorders

  • No preview · Conference Paper · Nov 2014
  • Akinori Okada · Haruki Koike · Tomohiko Nakamura · Masakatu Motomura · Gen Sobue
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    ABSTRACT: We evaluated the efficacy of intravenous immunoglobulin (IVIg) in a patient with Lambert-Eaton myasthenic syndrome (LEMS). Comprehensive clinical and electrophysiological testing was performed on a 34-year-old woman with progressive limb weakness, before and after IVIg treatment. Neurological examination revealed muscle weakness, predominantly in the proximal parts of the limbs. Muscle weakness improved following a short period of maximum voluntary muscle contraction. A repetitive low-rate (3-Hz) nerve stimulation test of the abductor hallucis was normal, but high-rate (20-Hz) stimulation induced an incremental response. Anti-presynaptic P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibodies were absent in the patient's serum. Whole body computed tomography revealed no tumors. We diagnosed seronegative LEMS without tumor and treated the patient with IVIg. Both clinical and electrophysiological indices improved gradually after treatment. This case study indicates that treatment with IVIg is equally effective for LEMS that is seronegative or seropositive for P/Q-VGCC antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.
    No preview · Article · Sep 2014 · Neuromuscular Disorders
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    ABSTRACT: Objective Olfactory dysfunction is considered to precede motor symptoms and early markers of Parkinson’s disease (PD), while the relative time at which cardiovascular dysautonomia appears in PD is not well understood. To assess the appearance of cardiovascular dysaunomomia in PD, we evaluated its relation to olfactory dysfunction in early-stage PD patients. Methods Twenty-three non-demented PD patients within 2 years from the onset of motor symptoms were enrolled. We evaluated olfactory dysfunction by the odor stick identification test for Japanese (OSIT-J) and analyzed its relationship to the results of other cardiovascular autonomic tests and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Results There was a correlation between olfactory scores and increased blood pressure in both the norepinephrine (r=0.75, p<0.0001, n=21) and dobutamine (r=0.57, p=0.0087, n=20) infusion tests and cardiac MIBG uptake (r=0.42, p=0.049, n=23). The fall in orthostatic blood pressure during the head-up tilt test was not correlated with the olfactory scores, but the Valsalva maneuver revealed that OSIT-J scores correlated with the pressure recovery time from phase III to the return of blood pressure to baseline (r=0.54, p=0.037, n=15) and with the magnitude of blood pressure overshoot during phase IV (r = 0.67, p = 0.0016, n=20). Conclusion Our results demonstrate that extensive components of the cardiovascular sympathetic system as well as the olfactory system are correlatively impaired in the early stage of PD, suggesting that degeneration of broad aspects of the cardiovascular sympathetic system occurs concurrently with olfactory system degeneration during the premotor phase of PD.
    No preview · Article · May 2014 · Parkinsonism & Related Disorders
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    ABSTRACT: Cardiac sympathetic denervation is associated with orthostatic hypotension (OH) in Parkinson's disease (PD); however, the physiological role of cardiac sympathetic nerves has yet to be elucidated. To clarify the role of the heart in orthostatic stress, we evaluated whether cardiac sympathetic nerves can alter cardiac activity and systolic blood pressure (BP) in association with elevations or depressions of total peripheral resistance during the head-up tilt test. Ninety-five PD patients and 17 normal controls were enrolled. Using impedance cardiography, we measured total peripheral resistance, stroke volume, heart rate, and systolic BP during the head-up tilt test. Cardiac denervation was defined as a heart-to-mediastinum ratio <1.7 for cardiac (123)I-metaiodobenzylguanidine uptake on delayed images. At 60° tilt, total peripheral resistance decreased from the initial value in 49 PD patients. Among these, 36 patients exhibited cardiac denervation with severe reductions in systolic BP but little change in stroke volume; among these patients 22 had OH. The remaining 13 patients without cardiac denervation exhibited significant increases in stroke volume and well-preserved systolic BP with no OH. On the other hand, 46 patients had elevations in total peripheral resistance and reduced stroke volume, but little change in systolic BP, regardless of the presence or absence of cardiac denervation. Only one of these patients experienced OH. Under orthostatic stress, cardiac sympathetic denervation with failure to increase total peripheral resistance leads to large reductions in systolic BP. However, patients without cardiac denervation exhibited a positive inotropic response against vasodilatation, which may prevent OH.
    No preview · Article · Jan 2014 · Parkinsonism & Related Disorders
  • Masaaki Hirayama · Tomohiko Nakamura · Gen Sobue
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    ABSTRACT: The clinical feature of Parkinson's disease (PD) is not based on the identification of the extrapyramidal symptom such as bradykinesia, restinbg tremor, rigidity, but also other non-motor symptom (REM sleep disorder, autonomic dysfunction, hyposmia etc). According to the cardio-sympathetic dysfunction, it is well known abnormal MIBG and orthostatic hypotension finding was seen in early disease stage. Furthermore denervation supersensitivity using β1 stimulant correlates the severity of MIBG image, so that this abnormal cardiac function induces inadequate cardiac capacity for exercise. Inadequate cardiac capacity makes easy fatigability, which correlates the abnormal MIBG image and cardio-sympathetic damage. So it is difficult to prescribe a specific exercise program to meet individual PD patients needs. Music therapy and trunk exercise (for example Tai-Chi exercise) are better suited for PD patients.
    No preview · Article · Dec 2013
  • Akinori Okada · Haruki Koike · Tomohiko Nakamura · Hirohisa Watanabe · Gen Sobue
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    ABSTRACT: Folate deficiency is known to be associated with subacute combined degeneration of the spinal cord; however, reports of long-standing cases are rare. Although neurological deficits due to folate deficiency have been reported to respond to folic acid supplementation, the functional outcomes have not been fully elucidated. The aim of the study was to evaluate the clinical features and response to folate supplementation in a patient with folate deficiency manifested over 10years as a slowly progressive myelopathy. We performed comprehensive clinical screening, electrophysiological testing, and posturography before and after folate supplementation. A 49-year-old man had a slowly progressive gait disturbance for 10years. He had not eaten fresh green vegetables for more than 10years. Neurological examination revealed spastic paraplegia and absence of any vibration sense in the lower limbs accompanied by a positive Romberg's sign. Serum folate level was low, and plasma homocysteine level was elevated. Levels of blood thiamine and serum cobalamin were normal. We diagnosed the patient with myelopathy due to folate deficiency. Folic acid supplementation led to improvement of his symptoms; posturography and walking speed tests showed partial improvement, while the somatosensory-evoked potentials and central motor conduction time remained unchanged. Folate deficiency should be considered as a differential diagnosis of chronic slowly progressive myelopathy. The present case suggests the importance of early diagnosis and treatment before the adverse neurological manifestations of folate deficiency become irreversible.
    No preview · Article · Oct 2013 · Journal of the neurological sciences
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    ABSTRACT: The aim of this study was to investigate the cortical and subcortical brain structures in Parkinson's disease (PD) with visual hallucination (VH), and to elucidate the association between the proposed hypothesis of VH in PD and regional brain volume changes. We used 3T magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to investigate the brain structures of PD patients with VH (PD-VH; n = 13) and PD patients without VH (PD-C; n = 13). The PD-VH patients showed significant cortical atrophy compared to the PD-C patients in the bilateral dorsolateral prefrontal cortex, left rostral region of the prefrontal cortex, left ventral section of the cingulate cortex, bilateral primary visual cortex, and secondary visual cortex including the left inferior occipital gyrus, right lingual cortex, right supramarginal gyrus, and left fusiform gyrus. Significant subcortical atrophic changes were observed in the white matter of the right parahippocampal gyrus, the bilateral posterior part of the cingulate gyrus, the left lingual gyrus, and the right middle occipital gyrus. VH in PD can occur due to distinctive neuroanatomical involvement. © 2013 International Parkinson and Movement Disorder Society.
    No preview · Article · Oct 2013 · Movement Disorders
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    ABSTRACT: Aims: Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3. The clinical manifestations of SCA3 include peripheral neuropathy, which is an important cause of disability in a subset of patients. Although the loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the cause of this neuropathy, the precise mechanism remains to be elucidated. Methods: To clarify the clinicopathological characteristics of SCA3-associated peripheral neuropathy, we performed nerve conduction studies and histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 patients. Immunohistochemical analyses of the anterior and posterior roots of the spinal cord and peripheral nerves were performed in five SCA3 patients. We also employed immunohistochemistry and immunoelectron microscopy analyses with an anti-polyglutamine antibody. Results: The mean sensory nerve action potentials of the SCA3 patients were half of the normal values. The motor conduction velocities were decreased, and the distal latencies were also significantly prolonged in the nerves studied relative to the those in normal controls. Histopathological analyses detected axonal sprouting and myelin thinning in all cases. Ataxin-3 aggregates were found in the cytoplasm of Schwann cells in all of the SCA3 patients examined but not in control subjects. Conclusions: In addition to the previously reported neuronopathy, the results of the present study indicate that Schwann cells are involved in the formation of the pathogenic intracytoplasmic ataxin-3 protein aggregates in patients with SCA3-associated neuropathy.
    No preview · Article · Apr 2013 · Neuropathology and Applied Neurobiology
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    ABSTRACT: Acute sensory ataxic neuropathy (ASAN) is known to occur with acute and monophasic sensory ataxia. Although autonomic dysfunctions have been reported, no detailed descriptions are currently available. We describe a case of ASAN in which the autonomic manifestations were systematically investigated. Although the patient did not complain of any autonomic symptoms, except for photophobia due to mydriasis, autonomic testing revealed widespread autonomic dysfunctions. Norepinephrine and dobutamine infusion test indicated the presence of sympathetic dysfunction. Additionally, the pupillary response to pilocarpine revealed the presence of parasympathetic dysfunction. In conclusion, widespread, subclinical autonomic dysfunctions may be present in ASAN patients.
    No preview · Article · Apr 2013 · Autonomic neuroscience: basic & clinical
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    ABSTRACT: Introduction: Information related to the long-term follow-up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. Methods: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. Results: Although the patient with late-onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early-onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early-onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. Conclusion: Aging may determine the progression of neuropathy after liver transplantation.
    No preview · Article · Dec 2012 · Muscle & Nerve
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    ABSTRACT: Background and purpose: Many non-motor symptoms are associated with Parkinson's disease (PD). Of these, pain and olfactory disturbance tend to be common premotor symptoms. PD has been shown to exhibit abnormal central pain processing, although underlying mechanisms are not yet fully understood. In order to investigate this further, we assessed PD patients by specific Aδ stimulation with intra-epidermal needle electrode and determined olfactory function. Methods: Forty-two patients (18 males and 24 females) with PD and 17 healthy control subjects (8 males and 9 females) were studied. A thin needle electrode was used to stimulate epidermal Aδ fibers, and somatosensory evoked potentials (SEPs) recorded at the vertex. Olfactory function was evaluated using the Odor Stick Identification Test for Japanese (OSIT-J) and its relationship with pain-related SEPs was investigated. Results: There were no significant differences in N1 latencies or P1 latencies although N1/P1 peak-to-peak amplitudes were significantly lower (p < 0.01) in PD patients than in control subjects. In PD patients, there were significant correlations between N1/P1 amplitudes and disease duration (r = -0.35, p < 0.05), Hoehn-Yahr stage (r = -0.38, p < 0.05) and UPDRS part III (r = -0.42, p < 0.01). Furthermore, the OSIT-J scores correlated with SEP amplitude (r = 0.41, p < 0.01). Conclusion: Pain processing in PD patients was impaired under specific nociceptive stimulation of Aδ fibers and significant correlation with smell dysfunction was detected. We suggest that this mechanism may involve the limbic system during PD pathology.
    No preview · Article · Jul 2012 · Parkinsonism & Related Disorders
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    ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron diseases. Sensory impairment is sometimes observed, and electrophysiological involvement has been described in the sensory nerves of SBMA patients. We hypothesized that a sensory nerve conduction study (NCS) could be used to discriminate SBMA from ALS. We compared the results from NCSs in a total of 120 SBMA cases confirmed by genetic analysis, 188 ALS cases, and 50 normal subjects. Sensory nerve action potential (SNAP) amplitudes of the SBMA group were significantly lower than in the ALS and control groups. In addition, receiver-operating characteristic curve analysis for SNAP amplitude showed that a cut-off value of 13.8 μV for median, 10.7 μV for ulnar, and 9.9 μV for sural nerve best discriminated SBMA from ALS. The specific decrease of SNAP amplitude in SBMA provides another useful tool for the differential diagnosis of motor neuron diseases.
    No preview · Article · Feb 2012 · Muscle & Nerve
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    ABSTRACT: We used accelerometry and visual examination by a neurologist to measure the intensity and frequency of hand tremor under resting, postural, writing, and walking conditions among patients with essential tremor with resting tremor (n=11) and Parkinson's disease (n=38). The intensity of essential tremor was markedly attenuated during walking relative to resting. The intensity and frequency of parkinsonian tremors were higher while walking than while resting. We suggest that assessment of the intensity and frequency of tremor during walking is clinically useful for differentiating between essential tremor with resting tremor and parkinsonian tremor, especially in the early stages, when the two conditions are often difficult to distinguish. Parkinsonian tremors are known to be enhanced during walking. Our clinical experience, as well as that of others, suggests that the intensity of essential tremor with resting tremor is markedly attenuated during walking.
    No preview · Article · Sep 2011 · Journal of Clinical Neuroscience
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    ABSTRACT: Patients with Parkinson's disease often complain of fatigue, and although cardiac sympathetic denervation is thought to be associated with fatigue, this link remains unclear. Previously, we detected cardiac sympathetic denervation in patients with Parkinson's disease using dobutamine, a selective beta-1 stimulant. To clarify the involvement of autonomic dysfunction in fatigue in Parkinson's disease, we conducted autonomic function tests on 33 patients with Parkinson's disease (mean age, 66.1 ± 5.6 years; 20 men, 13 women) and evaluated their relationships to fatigue. We divided patients into 2 groups, fatigued (n = 12) and nonfatigued (n = 21), based on an average score ≥ 3.3 on the Parkinson fatigue scale. Autonomic function tests included the coefficient of variation of R-R intervals, head-up tilt test, norepinephrine and dobutamine infusion tests, and cardiac (123) I-metaiodobenzylguanidine scintigraphy. The coefficient of variation of R-R intervals and the systolic blood pressure changes accompanying the head-up tilt test did not show significant differences between the 2 groups; however, the pressor responses in the norepinephrine and dobutamine infusion tests were significantly greater in the fatigued group than in the nonfatigued group. The (123) I-metaiodobenzylguanidine heart-to-mediastinal uptake ratio was lower in the fatigued group than in the nonfatigued group. Partial correlation analyses, using disease duration and Hoehn and Yahr stage as control variables, also demonstrated significant correlations between the Parkinson fatigue scale score and the results of the autonomic function tests and cardiac (123) I-metaiodobenzylguanidine uptake. Our results suggest that autonomic dysfunction, including cardiac sympathetic denervation, is associated with fatigue in patients with Parkinson's disease.
    No preview · Article · Aug 2011 · Movement Disorders
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    ABSTRACT: Oxidative stress is causally associated with the pathogenesis of Parkinson's disease (PD). Oxygen generates a large amount of reactive oxygen species (ROS). ROS including hydroxyl radicals and H(2)O(2) react with guanine residues in DNA and produce 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG serves as a biomarker for oxidative stress in various diseases. We investigated urinary 8-OHdG levels in 61 PD patients and 28 normal subjects to evaluate the correlation with various clinical features. We quantified disease severity using the Unified Parkinson's Disease Rating Scale for motor symptoms (UPDRS part 3), the Mini-Mental State Examination (MMSE) for mental function, and the Tottori University Hallucination Rating Scale (TUHARS) for quantifying hallucinations. There were significant correlations between 8-OHdG and all the examined parameters, but the partial correlation coefficients excluding contributions of all the other parameters showed that only TUHARS and UPDRS part 3 are significantly related to 8-OHdG. In particular, TUHARS correlates best with urinary 8-OHdG levels. The significant correlation between urinary 8-OHdG levels and hallucinations but not with dementia suggests that hallucinations are likely to have unique but unidentified mechanisms that lead to excessive production of 8-OHdG.
    No preview · Article · Jan 2011 · Parkinsonism & Related Disorders
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    ABSTRACT: We investigated 17 patients with sporadic amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) and voxel-based analysis of diffusion tensor images (DTI) at baseline and after a six-month follow-up. Compared with 17 healthy controls, ALS patients at baseline showed only minimal white matter volume decreases in the inferior frontal gyrus but marked decreases in the gray matter of several regions, especially in the bilateral paracentral lobule of the premotor cortex. DTI revealed reduced fractional anisotropy in the bilateral corticospinal tracts, insula, ventrolateral premotor cortex, and parietal cortex. Increased mean diffusivity was noted bilaterally in the motor cortex, ventrolateral premotor cortex, insula, hippocampal formation, and temporal gyrus. At the six-month follow-up, ALS patients showed widespread volume decreases in gray matter, and DTI abnormalities extended mainly into the bilateral frontal lobes, while volume changes in the white matter remained minimal but more distinct. Our combined VBM and DTI techniques revealed extra-corticospinal tract neuronal degeneration mainly in the frontotemporal lobe of ALS patients. In particular, follow-up examinations in these patients showed that whole-brain DTI changes occurred predominantly in the regions of brain atrophy. These objective analyses can be used to assess the disease condition of the ALS brain.
    No preview · Article · Jan 2011 · Amyotrophic Lateral Sclerosis
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    ABSTRACT: To characterize the morphological progression of neuropathy associated with immunoglobulin M-monoclonal gammopathy of undetermined significance with anti-myelin-associated glycoprotein antibody, we assessed histopathologic features of sural nerve specimens from 15 patients, emphasizing widely spaced myelin (WSM), demyelination, and tomaculous changes. The frequency of WSM correlated with that of demyelination and tomaculous appearance in teased-fiber preparations. In longitudinal sections at nodes of Ranvier and paranodal regions, the spaces between terminal myelin loops, particularly those adjacent to the node of Ranvier, were widened, indicating an early change before demyelination, and there was concomitant swelling of terminal myelin loops. Some conspicuously swollen terminal myelin loops were detached from the paranodal axolemma, thereby widening the nodes of Ranvier. Tomacula coexisted frequently with redundant myelin loops and WSM, particularly in the outermost layer of myelin sheaths, suggesting that loosening of the outer layers contributes to their formation. By immunofluorescence microscopy, immunoglobulin M and myelin-associated glycoprotein were colocalized in paranodal regions and Schmidt-Lanterman incisures. Confocal analysis revealed colocalization of immunoglobulin M and complement product C3d corresponding to the area of WSM. Thus, morphological changes in terminal myelin loops, formation of WSM at paranodes, and subsequent dissociation from paranodal axolemma (which may be associated with activation of the complement pathway) likely contribute to demyelination in this condition. Loosening of compact myelin seems to contribute to tomacula formation.
    No preview · Article · Oct 2010 · Journal of Neuropathology and Experimental Neurology