Journal of neuropathology and experimental neurology, Jan 15, 2016
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARA... more Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1 The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations result in vascular changes. Ten homozygous, 1 compound heterozygous, and 1 homozygous frameshift mutation have been identified in the HTRA1 gene of patients with genetically confirmed CARASIL. However, few studies have compared neuropathologic findings in patients with the same or different mutations in HTRA1 We analyzed histopathologic alterations in 3 autopsied patients with genetically confirmed CARASIL: 2 of them had the HTRA1 p.R302X mutation and 1 had the HTRA1 p.A252T mutation. All 3 had similar cerebral arteriopathy showing myointimal proliferation, multi-layering and splitting of elastic laminae, and marked loss of medial smooth muscle cells. One CARASIL patient...
To investigate the need for pre- and post-graduate education for neurologists, the subcommittee o... more To investigate the need for pre- and post-graduate education for neurologists, the subcommittee of the Japanese Society of Neurology for education performed a questionnaire-based survey in 80 medical universities throughout Japan. The response rate to the questionnaire was 82.5%. Textbooks for lectures for medical students were used in only 22.7% of those universities. If the Japanese Society of Neurology (JSN) made a standard text, 77.8% of universities would like to use it. Most of the training programs for residents were compatible with the minimum requirements of the JSN. Just 66.7% of those training programs were completed in their own institute, and 77.3% of universities required help from the JSN.
We reported two patients with neurocutaneous angiomatosis. Patient 1, a 36-year-old woman of Cobb... more We reported two patients with neurocutaneous angiomatosis. Patient 1, a 36-year-old woman of Cobb syndrome had cutaneous portwine angiomas in the high back and spinal arteriovenous malformations at the level of Th4-11. She had also atrophy and livedo reticularis presenting during standing position in the left lower extremity. Patient 2, a 47-year-old man of Klippel-Trenaunay-Weber syndrome had varices in the bilateral lower extremities, cutaneous portwine angiomas in the high back and bilateral lower extremities, and hypertrophy of the bilateral legs. Neuroradiological examination revealed abnormal vessels in the spinal canal at the level of C5 and Th4. These syndromes may have no essential difference because of the presence of neural and cutaneous angiomas at the corresponding level, venous system disorders and trophic changes (hypertrophy/atrophy).
We reviewed MRI findings in 22 patients (37 cases) with clinically diagnosed multiple sclerosis (... more We reviewed MRI findings in 22 patients (37 cases) with clinically diagnosed multiple sclerosis (MS) with spinal cord lesions. The spinal cord lesions were detected in 17 (46%) of these 37 cases on MRI. The cervical cord lesions were more detectable than other spinal cord lesions. At the thoracic level, the upper lesions were more detectable than the lower ones. In this study, no correlation was found between the disease duration, the rate of functional disturbance and the detectable rate of spinal cord lesions. The characteristic findings of the lesions were swelling and the enhancement effect of Gd-DTPA in the patient group with a disease duration of less than three years, and atrophic change in the patient group with a disease duration of greater than seven years. The period of the enhancement effect of Gd-DTPA varied in each case, and it may reflect the clinical course. Syrinx-like lesions were found in four cases. In one of them, atrophic change was found in the same region six months after the follow up study. Although the precise reason for the syrinx-like lesion was unclear, a relationship between syrinx-like lesion and atrophy of the spinal cord was suggested. The MRI findings of the spinal cord lesions in MS varied in each case and in each stage of the disease.
We report two cases in which neurological examination met the Second Tentative Criteria for Brain... more We report two cases in which neurological examination met the Second Tentative Criteria for Brain Death of Chiba University Medical School, except for spontaneous contractions of the rectus abdominis muscle during apnea testing. In Case 1, a 54-year-old man with brainstem infarction, judgement of brain death was suspended initially, but was ultimately declared after the contractions were deemed to be spinal in origin. MRI findings after declaration and autopsy were compatible with brain death. In Case 2, a 27-year-old man with fulminant hepatitis and subsequent severe brain edema, judgement was postponed due to detection of the contractions at the second testing, and was ceased with family intent. Several cases of abnormal gross and fine movements in brain-dead patients have been reported. These paradoxical phenomena may confuse an inexperienced examiner and delay the declaration of brain death. Whether brain death should be considered real death of the person or not, neurologists should be aware of the occasional presence of neurological problems in the diagnosis of brain death, such as spinally-mediated movements. Since the major opposition to brain death is the distrust of medical doctors, we propose a pilot system of a "brain death judging doctor".
Adrenomyeloneuropathy (AMN), a clinical variant of child adrenoleukodystrophy (ALD), is an adult-... more Adrenomyeloneuropathy (AMN), a clinical variant of child adrenoleukodystrophy (ALD), is an adult-onset progressive disorder which presents spastic paraparesis with peripheral nerve involvement and affects mainly the pyramidal tracts from the brainstem to the spinal cord. We report a case of AMN in which serial MRI showed unusual development of areas of high signal in the right striatum. The patient was in good health until the age of 12, when he began to lose his hair. At age 25 he started to have progressive gait disturbance and erectile impotence. In his first admission to our hospital at age 33, he showed diffuse baldness. He was intelligent but childish. His cranial nerves were normal. Muscle strength was weak (3-4/5) in the lower extremities. Deep tendon reflexes were hyperactive in the lower extremities while normal in the upper extremities. Babinski signs were elicited bilaterally. Pinprick and vibratory sensation was impaired in the lower legs. Proprioceptive sensations were normal. Co-ordination was intact. There were urinary incontinence and impairment of erection with preserved libido and ejaculation. Routine laboratory data including hematological studies, serum chemistry and urinalysis were all normal except for mild hyperlipidemia. Serum cortisol response to ACTH was low and serum levels of very long chain fatty acids were increased. Nerve conduction studies were abnormal and consistent with peripheral polyneuropathy. A biopsy specimen of left sural nerve revealed a mild loss of myelinated fibers with thinning of the myelin. These findings and the clinical features confirmed the diagnosis of AMN. MRI in SE2000/40 scans at age 34 disclosed areas of high signal in the bilateral internal capsules.(ABSTRACT TRUNCATED AT 250 WORDS)
A 67-year-old woman developed central pain in the face with bilateral horizontal gaze palsy follo... more A 67-year-old woman developed central pain in the face with bilateral horizontal gaze palsy following brainstem encephalitis. Magnetic resonance imaging demonstrated a lesion in the pontobulbar tegmental area.
Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space... more Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space. In the previous study (Hirayama, Fukutake, et al., 1986), we demonstrated that such kind of proprioception, which we called "proprioceptive localization", could be detected by making the patient pick up the thumb with the opposite fingers (the thumb localizing test, TLT). As a further development of the TLT, another test, named a big-toe localizing test (BTLT), was devised. In the BTLT, the patient, with eyes closed and a lower limb passively immobilized by the examiner (the fixed limb), is asked to point to the big toe with the index finger of one hand or the other (the reaching limb). Firstly, we assessed the unselected series of 33 patients with thoracic or lumbar myelopathy regarding their sensory impairment and obtained the following conclusions on the BTLT similar to those in our previous study on the TLT. (1) BTLT deficits results from perceptive impairment in the fixed limb. (2) The perceptual information involved in the proprioceptive localization is different from that of the test for the appreciation of passive movement and posture. (3) On the basis of the correlation to other symptomatology, it is suggested that BTLT deficits arise from lesions of the posterior column-medical lemniscal system. (4) The BTLT is more sensitive than the test for the appreciation of passive movement and posture. Secondly, we evaluated another unselected series of 63 patients with unilateral TLT deficits due to CNS lesions. Eight patterns of BTLT deficits were identified and classified into 3 following types.(ABSTRACT TRUNCATED AT 250 WORDS)
Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is percei... more Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is perceived to be at the corresponding area on the opposite side. In our previous study (Kawamura, Hirayama et al., 1987), we suggested that it may be useful for localization because this phenomenon was observed most frequently in patients with a right putaminal hemorrhage of medium or large size, an average of 42 ml on CT scans, presenting a slight disturbance of consciousness and, in about half of the patients, anosognosia. We also suggested that since alloesthesia is produced not only in cerebral but also in spinal cord lesions, it seems to represent an elementary sensory disturbance of sensory pathways, not a higher cortical dysfunction. We recently observed alloesthesia in two other patients with smaller right putaminal hemorrhages, 7 ml and 6 ml, respectively, who exhibited no disturbance of consciousness, but had impairment not only of superficial but also of proprioceptive sensations. In Patient 1, superficial sensations were intact on admission, except those on the left side of the face. Cortical somatosensory evoked potentials (SEPs) after stimulating the median nerve were measured on Patient 1 on the 11th hospital day when a left hemihypalgesia had developed due to enlargement of the hematoma from 7 to 14 ml. Stimulation of the clinically affected side (left) evoked no N20 from the contralateral scalp. Right-sided stimulation was normal. The fact that both patients showed alloesthesia with no accompanying disturbance of consciousness supported our view of its mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of neuropathology and experimental neurology, Jan 15, 2016
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARA... more Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1 The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations result in vascular changes. Ten homozygous, 1 compound heterozygous, and 1 homozygous frameshift mutation have been identified in the HTRA1 gene of patients with genetically confirmed CARASIL. However, few studies have compared neuropathologic findings in patients with the same or different mutations in HTRA1 We analyzed histopathologic alterations in 3 autopsied patients with genetically confirmed CARASIL: 2 of them had the HTRA1 p.R302X mutation and 1 had the HTRA1 p.A252T mutation. All 3 had similar cerebral arteriopathy showing myointimal proliferation, multi-layering and splitting of elastic laminae, and marked loss of medial smooth muscle cells. One CARASIL patient...
To investigate the need for pre- and post-graduate education for neurologists, the subcommittee o... more To investigate the need for pre- and post-graduate education for neurologists, the subcommittee of the Japanese Society of Neurology for education performed a questionnaire-based survey in 80 medical universities throughout Japan. The response rate to the questionnaire was 82.5%. Textbooks for lectures for medical students were used in only 22.7% of those universities. If the Japanese Society of Neurology (JSN) made a standard text, 77.8% of universities would like to use it. Most of the training programs for residents were compatible with the minimum requirements of the JSN. Just 66.7% of those training programs were completed in their own institute, and 77.3% of universities required help from the JSN.
We reported two patients with neurocutaneous angiomatosis. Patient 1, a 36-year-old woman of Cobb... more We reported two patients with neurocutaneous angiomatosis. Patient 1, a 36-year-old woman of Cobb syndrome had cutaneous portwine angiomas in the high back and spinal arteriovenous malformations at the level of Th4-11. She had also atrophy and livedo reticularis presenting during standing position in the left lower extremity. Patient 2, a 47-year-old man of Klippel-Trenaunay-Weber syndrome had varices in the bilateral lower extremities, cutaneous portwine angiomas in the high back and bilateral lower extremities, and hypertrophy of the bilateral legs. Neuroradiological examination revealed abnormal vessels in the spinal canal at the level of C5 and Th4. These syndromes may have no essential difference because of the presence of neural and cutaneous angiomas at the corresponding level, venous system disorders and trophic changes (hypertrophy/atrophy).
We reviewed MRI findings in 22 patients (37 cases) with clinically diagnosed multiple sclerosis (... more We reviewed MRI findings in 22 patients (37 cases) with clinically diagnosed multiple sclerosis (MS) with spinal cord lesions. The spinal cord lesions were detected in 17 (46%) of these 37 cases on MRI. The cervical cord lesions were more detectable than other spinal cord lesions. At the thoracic level, the upper lesions were more detectable than the lower ones. In this study, no correlation was found between the disease duration, the rate of functional disturbance and the detectable rate of spinal cord lesions. The characteristic findings of the lesions were swelling and the enhancement effect of Gd-DTPA in the patient group with a disease duration of less than three years, and atrophic change in the patient group with a disease duration of greater than seven years. The period of the enhancement effect of Gd-DTPA varied in each case, and it may reflect the clinical course. Syrinx-like lesions were found in four cases. In one of them, atrophic change was found in the same region six months after the follow up study. Although the precise reason for the syrinx-like lesion was unclear, a relationship between syrinx-like lesion and atrophy of the spinal cord was suggested. The MRI findings of the spinal cord lesions in MS varied in each case and in each stage of the disease.
We report two cases in which neurological examination met the Second Tentative Criteria for Brain... more We report two cases in which neurological examination met the Second Tentative Criteria for Brain Death of Chiba University Medical School, except for spontaneous contractions of the rectus abdominis muscle during apnea testing. In Case 1, a 54-year-old man with brainstem infarction, judgement of brain death was suspended initially, but was ultimately declared after the contractions were deemed to be spinal in origin. MRI findings after declaration and autopsy were compatible with brain death. In Case 2, a 27-year-old man with fulminant hepatitis and subsequent severe brain edema, judgement was postponed due to detection of the contractions at the second testing, and was ceased with family intent. Several cases of abnormal gross and fine movements in brain-dead patients have been reported. These paradoxical phenomena may confuse an inexperienced examiner and delay the declaration of brain death. Whether brain death should be considered real death of the person or not, neurologists should be aware of the occasional presence of neurological problems in the diagnosis of brain death, such as spinally-mediated movements. Since the major opposition to brain death is the distrust of medical doctors, we propose a pilot system of a "brain death judging doctor".
Adrenomyeloneuropathy (AMN), a clinical variant of child adrenoleukodystrophy (ALD), is an adult-... more Adrenomyeloneuropathy (AMN), a clinical variant of child adrenoleukodystrophy (ALD), is an adult-onset progressive disorder which presents spastic paraparesis with peripheral nerve involvement and affects mainly the pyramidal tracts from the brainstem to the spinal cord. We report a case of AMN in which serial MRI showed unusual development of areas of high signal in the right striatum. The patient was in good health until the age of 12, when he began to lose his hair. At age 25 he started to have progressive gait disturbance and erectile impotence. In his first admission to our hospital at age 33, he showed diffuse baldness. He was intelligent but childish. His cranial nerves were normal. Muscle strength was weak (3-4/5) in the lower extremities. Deep tendon reflexes were hyperactive in the lower extremities while normal in the upper extremities. Babinski signs were elicited bilaterally. Pinprick and vibratory sensation was impaired in the lower legs. Proprioceptive sensations were normal. Co-ordination was intact. There were urinary incontinence and impairment of erection with preserved libido and ejaculation. Routine laboratory data including hematological studies, serum chemistry and urinalysis were all normal except for mild hyperlipidemia. Serum cortisol response to ACTH was low and serum levels of very long chain fatty acids were increased. Nerve conduction studies were abnormal and consistent with peripheral polyneuropathy. A biopsy specimen of left sural nerve revealed a mild loss of myelinated fibers with thinning of the myelin. These findings and the clinical features confirmed the diagnosis of AMN. MRI in SE2000/40 scans at age 34 disclosed areas of high signal in the bilateral internal capsules.(ABSTRACT TRUNCATED AT 250 WORDS)
A 67-year-old woman developed central pain in the face with bilateral horizontal gaze palsy follo... more A 67-year-old woman developed central pain in the face with bilateral horizontal gaze palsy following brainstem encephalitis. Magnetic resonance imaging demonstrated a lesion in the pontobulbar tegmental area.
Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space... more Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space. In the previous study (Hirayama, Fukutake, et al., 1986), we demonstrated that such kind of proprioception, which we called "proprioceptive localization", could be detected by making the patient pick up the thumb with the opposite fingers (the thumb localizing test, TLT). As a further development of the TLT, another test, named a big-toe localizing test (BTLT), was devised. In the BTLT, the patient, with eyes closed and a lower limb passively immobilized by the examiner (the fixed limb), is asked to point to the big toe with the index finger of one hand or the other (the reaching limb). Firstly, we assessed the unselected series of 33 patients with thoracic or lumbar myelopathy regarding their sensory impairment and obtained the following conclusions on the BTLT similar to those in our previous study on the TLT. (1) BTLT deficits results from perceptive impairment in the fixed limb. (2) The perceptual information involved in the proprioceptive localization is different from that of the test for the appreciation of passive movement and posture. (3) On the basis of the correlation to other symptomatology, it is suggested that BTLT deficits arise from lesions of the posterior column-medical lemniscal system. (4) The BTLT is more sensitive than the test for the appreciation of passive movement and posture. Secondly, we evaluated another unselected series of 63 patients with unilateral TLT deficits due to CNS lesions. Eight patterns of BTLT deficits were identified and classified into 3 following types.(ABSTRACT TRUNCATED AT 250 WORDS)
Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is percei... more Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is perceived to be at the corresponding area on the opposite side. In our previous study (Kawamura, Hirayama et al., 1987), we suggested that it may be useful for localization because this phenomenon was observed most frequently in patients with a right putaminal hemorrhage of medium or large size, an average of 42 ml on CT scans, presenting a slight disturbance of consciousness and, in about half of the patients, anosognosia. We also suggested that since alloesthesia is produced not only in cerebral but also in spinal cord lesions, it seems to represent an elementary sensory disturbance of sensory pathways, not a higher cortical dysfunction. We recently observed alloesthesia in two other patients with smaller right putaminal hemorrhages, 7 ml and 6 ml, respectively, who exhibited no disturbance of consciousness, but had impairment not only of superficial but also of proprioceptive sensations. In Patient 1, superficial sensations were intact on admission, except those on the left side of the face. Cortical somatosensory evoked potentials (SEPs) after stimulating the median nerve were measured on Patient 1 on the 11th hospital day when a left hemihypalgesia had developed due to enlargement of the hematoma from 7 to 14 ml. Stimulation of the clinically affected side (left) evoked no N20 from the contralateral scalp. Right-sided stimulation was normal. The fact that both patients showed alloesthesia with no accompanying disturbance of consciousness supported our view of its mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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