We treated three patients with subacute sclerosing panencephalitis with intraventricular interfer... more We treated three patients with subacute sclerosing panencephalitis with intraventricular interferon-alpha and oral inosiplex, and followed their clinical courses. One patient was also treated with ribavirin. Results were unsatisfactory; no significant clinical improvement was seen in the patients, and a number of serious complications occurred. Malfunction of the Ommaya reservoir, septic meningitis and chemical encephalopathy were observed in the three patients, respectively. The use of intraventricular interferon-alpha and ribavirin therapy has been increasing despite insufficient evidence of its efficacy. A high risk of serious side effects exists with this therapy. Thus it is important to consider not only the effects but also the side effects and complications as described above. We also propose that a standard protocol for the use of interferon-alpha and ribavirin and the cessation of current therapy is necessary.
The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with i... more The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with intractable epilepsy who was treated by surgical interventions. Magnetic resonance imaging (MRI) showed ambiguous corticomedullary boundary in the left frontal lobe, and magnetoencephalography (MEG) revealed spike dipoles in the vicinity of the left ventral striatum. The epileptic seizures disappeared after partial resection of the frontal lobe, but recurred within 2 months and remained intractable. Neuropathological examination confirmed the presence of focal cortical dysplasia in the resected brain tissue. Ictal single photon emission computed tomography at this period displayed hyperperfusion of the left anterior striatum. At the second surgery, intraoperative electrocorticography exhibited spike discharges from the anterior striatum. After the removal of this structure and adjacent brain tissues, the patient remains seizure-free for 33 months, without any neurological deficits. Histopathological examination of the resected tissue revealed a large number of dysmorphic neurons distributed widely in the cerebral cortex, subcortical white matter, striatum, and insular cortex. These findings suggest that microscopic dysplasia of basal ganglia can accompany certain cases of focal cortical malformations, and may play a critical role in the epileptogenesis through their interaction with cortical structures.
Epileptic disorders : international epilepsy journal with videotape, Jan 27, 2015
We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusi... more We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusing on high-voltage slow waves during ictal EEG. We studied 22 patients with epileptic spasms recorded during digital video-scalp EEG, including five individuals who still had persistent spasms after callosotomy. We analysed the duration, amplitude, latency to onset of electromyographic bursts, and distribution of the highest positive and negative peaks of slow waves in 352 spasms. High-voltage positive slow waves preceded the identifiable muscle contractions of spasms. The mean duration of these positive waves was 569±228 m, and the mean latency to electromyographic onset was 182±127 m. These parameters varied markedly even within a patient. The highest peak of the positive component was distributed in variable regions, which was not consistent with the location of lesions on MRI. The peak of the negative component following the positivity was distributed in the neighbouring or opposite ...
We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at... more We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been reported in cases of post-herpetic and other neuralgia as well as in cases of primary headaches in adulthood. This agent may also be promising for the treatment of intractable primary headaches during childhood.
The aim of the study was to understand the long-term health issues and potential predictors of ca... more The aim of the study was to understand the long-term health issues and potential predictors of cardiopulmonary arrest (CPA) in patients with severe childhood-onset psychomotor impairments. In this single-center, retrospective observational study, the medical records of 140 patients with severe childhood-onset psychomotor impairments were reviewed. The medical interventions and functional status of patients with a history of CPA (n=22: 14M/8F; mean±SD age: 26.6±12.4years) were compared with age- and sex-matched patients without a history of CPA (n=44: 28M/16F; mean±SD age: 26.5±12.3years). The prevalence of CPA was 15.7%. The most frequent cause was respiratory issues, and CPA occurred most frequently between 0 and 5years old. The patients who had a history of CPA were more likely to have required a feeding tube (p=0.0007), tracheostomy (p<0.0001), and ventilator (p=0.002) compared to the non-CPA patients, while the prevalence of tracheostomy or ventilator treatment during early i...
Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected i... more Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.
An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovar... more An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This ca...
Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and hea... more Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should ...
Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and hea... more Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should be monitored.
A newborn baby boy presented with giant melanocytic nevi on the face, trunk and extremities, and ... more A newborn baby boy presented with giant melanocytic nevi on the face, trunk and extremities, and focal cortical dysplasia on MRI. At 3 months of age, he developed intractable epilepsy, and MRI at 2 years of age revealed a high-intensity area in the bilateral cerebellum on T1-weighted images, indicative of melanosis. Based on the findings of the skin and MRI, we diagnosed the boy with neurocutaneous melanosis. Cytodiagnosis of cerebrospinal fluid showed no malignancies. EEG, magnetoencephalogram and ECD-SPECT indicated that the clonic seizures originated from a focus in the right focal cortical dysplasia. Complications also included sebaceous nevus of the head and face, which was characteristic of sebaceous nevus syndrome, lipoma of the face and cauda equina, and limbal dermoid. Sebaceous nevus syndrome may have been due to certain allelic defects that were independent of those for neurocutaneous melanosis.
Chronic unilateral pleural effusion developed in three patients with severe motor and intellectua... more Chronic unilateral pleural effusion developed in three patients with severe motor and intellectual disabilities. All patients received 5-15 years of dantrolene administration for their spasticity. The cause of pleural effusion was indistinct, despite close investigations for etiologies such as infection or tumor. The pleural fluid consisted of sterile exudate in all patients. One patient had eosinophilia in his pleural fluid, while peripheral blood eosinophilia was seen in the other two. The pleural biopsy and autopsy specimens revealed only non-specific inflammatory findings. After dantrolene therapy was discontinued, pleural effusion almost disappeared in two patients in the following several months, but the other died of multi-organ failure from another underlying disease. It is important to take chemical pleurisy into consideration when dealing with pleural effusion of unknown etiology. Moreover, respiratory side effect should be examined in patients treated with chronic dantrol...
Möbius syndrome is a rare disorder characterized by congenital bilateral facial nerve palsy. Abdu... more Möbius syndrome is a rare disorder characterized by congenital bilateral facial nerve palsy. Abducent palsy or other cranial nerve palsy, facial malformations, limb malformations, and skeletal malformations are common features associated with this syndrome. We report a 9-month-old infant in whom congenital muscular disorder was previously suspected because of facial muscle involvement (mask-like face), respiratory and swallowing disturbances, and hypotonia since birth. After an improvement in the respiratory infection, she showed slightly exaggerated deep tendon reflexes and an improvement in muscle tone. The occurrence of combined facial nerve palsy, glossopharyngeal nerve palsy, vagus nerve palsy, and hypoglossal nerve palsy strongly suggested that she had Möbius syndrome. Finally, the absence of the roots of bilateral facial nerves on an MRI confirmed that the disorder was Möbius syndrome. We propose that a thin slice MRI should be obtained to observe the cranial nerves around th...
We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at... more We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been ...
We treated three patients with subacute sclerosing panencephalitis with intraventricular interfer... more We treated three patients with subacute sclerosing panencephalitis with intraventricular interferon-alpha and oral inosiplex, and followed their clinical courses. One patient was also treated with ribavirin. Results were unsatisfactory; no significant clinical improvement was seen in the patients, and a number of serious complications occurred. Malfunction of the Ommaya reservoir, septic meningitis and chemical encephalopathy were observed in the three patients, respectively. The use of intraventricular interferon-alpha and ribavirin therapy has been increasing despite insufficient evidence of its efficacy. A high risk of serious side effects exists with this therapy. Thus it is important to consider not only the effects but also the side effects and complications as described above. We also propose that a standard protocol for the use of interferon-alpha and ribavirin and the cessation of current therapy is necessary.
The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with i... more The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with intractable epilepsy who was treated by surgical interventions. Magnetic resonance imaging (MRI) showed ambiguous corticomedullary boundary in the left frontal lobe, and magnetoencephalography (MEG) revealed spike dipoles in the vicinity of the left ventral striatum. The epileptic seizures disappeared after partial resection of the frontal lobe, but recurred within 2 months and remained intractable. Neuropathological examination confirmed the presence of focal cortical dysplasia in the resected brain tissue. Ictal single photon emission computed tomography at this period displayed hyperperfusion of the left anterior striatum. At the second surgery, intraoperative electrocorticography exhibited spike discharges from the anterior striatum. After the removal of this structure and adjacent brain tissues, the patient remains seizure-free for 33 months, without any neurological deficits. Histopathological examination of the resected tissue revealed a large number of dysmorphic neurons distributed widely in the cerebral cortex, subcortical white matter, striatum, and insular cortex. These findings suggest that microscopic dysplasia of basal ganglia can accompany certain cases of focal cortical malformations, and may play a critical role in the epileptogenesis through their interaction with cortical structures.
Epileptic disorders : international epilepsy journal with videotape, Jan 27, 2015
We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusi... more We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusing on high-voltage slow waves during ictal EEG. We studied 22 patients with epileptic spasms recorded during digital video-scalp EEG, including five individuals who still had persistent spasms after callosotomy. We analysed the duration, amplitude, latency to onset of electromyographic bursts, and distribution of the highest positive and negative peaks of slow waves in 352 spasms. High-voltage positive slow waves preceded the identifiable muscle contractions of spasms. The mean duration of these positive waves was 569±228 m, and the mean latency to electromyographic onset was 182±127 m. These parameters varied markedly even within a patient. The highest peak of the positive component was distributed in variable regions, which was not consistent with the location of lesions on MRI. The peak of the negative component following the positivity was distributed in the neighbouring or opposite ...
We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at... more We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been reported in cases of post-herpetic and other neuralgia as well as in cases of primary headaches in adulthood. This agent may also be promising for the treatment of intractable primary headaches during childhood.
The aim of the study was to understand the long-term health issues and potential predictors of ca... more The aim of the study was to understand the long-term health issues and potential predictors of cardiopulmonary arrest (CPA) in patients with severe childhood-onset psychomotor impairments. In this single-center, retrospective observational study, the medical records of 140 patients with severe childhood-onset psychomotor impairments were reviewed. The medical interventions and functional status of patients with a history of CPA (n=22: 14M/8F; mean±SD age: 26.6±12.4years) were compared with age- and sex-matched patients without a history of CPA (n=44: 28M/16F; mean±SD age: 26.5±12.3years). The prevalence of CPA was 15.7%. The most frequent cause was respiratory issues, and CPA occurred most frequently between 0 and 5years old. The patients who had a history of CPA were more likely to have required a feeding tube (p=0.0007), tracheostomy (p<0.0001), and ventilator (p=0.002) compared to the non-CPA patients, while the prevalence of tracheostomy or ventilator treatment during early i...
Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected i... more Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.
An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovar... more An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This ca...
Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and hea... more Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should ...
Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and hea... more Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should be monitored.
A newborn baby boy presented with giant melanocytic nevi on the face, trunk and extremities, and ... more A newborn baby boy presented with giant melanocytic nevi on the face, trunk and extremities, and focal cortical dysplasia on MRI. At 3 months of age, he developed intractable epilepsy, and MRI at 2 years of age revealed a high-intensity area in the bilateral cerebellum on T1-weighted images, indicative of melanosis. Based on the findings of the skin and MRI, we diagnosed the boy with neurocutaneous melanosis. Cytodiagnosis of cerebrospinal fluid showed no malignancies. EEG, magnetoencephalogram and ECD-SPECT indicated that the clonic seizures originated from a focus in the right focal cortical dysplasia. Complications also included sebaceous nevus of the head and face, which was characteristic of sebaceous nevus syndrome, lipoma of the face and cauda equina, and limbal dermoid. Sebaceous nevus syndrome may have been due to certain allelic defects that were independent of those for neurocutaneous melanosis.
Chronic unilateral pleural effusion developed in three patients with severe motor and intellectua... more Chronic unilateral pleural effusion developed in three patients with severe motor and intellectual disabilities. All patients received 5-15 years of dantrolene administration for their spasticity. The cause of pleural effusion was indistinct, despite close investigations for etiologies such as infection or tumor. The pleural fluid consisted of sterile exudate in all patients. One patient had eosinophilia in his pleural fluid, while peripheral blood eosinophilia was seen in the other two. The pleural biopsy and autopsy specimens revealed only non-specific inflammatory findings. After dantrolene therapy was discontinued, pleural effusion almost disappeared in two patients in the following several months, but the other died of multi-organ failure from another underlying disease. It is important to take chemical pleurisy into consideration when dealing with pleural effusion of unknown etiology. Moreover, respiratory side effect should be examined in patients treated with chronic dantrol...
Möbius syndrome is a rare disorder characterized by congenital bilateral facial nerve palsy. Abdu... more Möbius syndrome is a rare disorder characterized by congenital bilateral facial nerve palsy. Abducent palsy or other cranial nerve palsy, facial malformations, limb malformations, and skeletal malformations are common features associated with this syndrome. We report a 9-month-old infant in whom congenital muscular disorder was previously suspected because of facial muscle involvement (mask-like face), respiratory and swallowing disturbances, and hypotonia since birth. After an improvement in the respiratory infection, she showed slightly exaggerated deep tendon reflexes and an improvement in muscle tone. The occurrence of combined facial nerve palsy, glossopharyngeal nerve palsy, vagus nerve palsy, and hypoglossal nerve palsy strongly suggested that she had Möbius syndrome. Finally, the absence of the roots of bilateral facial nerves on an MRI confirmed that the disorder was Möbius syndrome. We propose that a thin slice MRI should be obtained to observe the cranial nerves around th...
We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at... more We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been ...
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Papers by Eiji Nakagawa