Tetsuzo Tagawa

Zonisamide Monotherapy in Newly Diagnosed Infantile Spasms

Summary: Purpose: We determined the short‐term efficacy of zonisamide (ZNS) monotherapy in newly diagnosed patients with infantile spasms (IS).

Primitive Reflex Profiles in Infants: Differences Based on Categories of Neurological Abnormality

In order to clarify reflex profiles in the first year of life in connection with categories of neurological abnormality, six primitive reflexes, i.e., the crossed extensor reflex, suprapubic extensor reflex, heel reflex, Galant response, asymmetric tonic neck reflex and plantar grasp response, were examined in 458 normal infants, 78 infants with cerebral palsy (CP) and 81 infants with mental retardation (MR), whose diagnoses were confirmed at a later follow-up examination. The change in the mean score for each of these reflexes with age was characteristic for each category or type of neurological abnormality. This implies that a presumptive diagnosis can be made in neurologically high-risk infants by examination of the primitive reflexes. Such reflexes are therefore of specific significance, among other neurological criteria, in infants within the first year of life.

Hypomelanosis of Ito associated with hemimegalencephaly: A clinicopathological study

A girl with hypomelanosis of Ito was studied both clinically and at postmortem examination. She manifested severe epilepsy early after birth. Magnetic resonance imaging demonstrated left-sided hemimegalencephaly. The seizures were secondarily generalized or unilateral initially, followed by infantile spasms with asymmetrical hypsarrhythmia at 1.5 months of age. Frequent complex partial seizures, refractory to anti-epileptic drug treatments appeared at 4 months of age. She died of pneumonia at the age of 14 months. Postmortem examination revealed marked asymmetry of the cerebrum and gyral abnormalities in the left cerebral hemisphere. Histopathologically, severe disorganization of the neuronal cytoarchitecture was evident. Absence of delineation between cortical gray and white matter was evident, as was increase and hypertrophy of the neurons and glial cells. We believe that the association of skin and brain lesions was not one of chance; that is, they may share a common pathogenetic mechanism.

Pure red cell aplasia during carbamazepine monotherapy

A 7-year-old girl developed pure red cell aplasia during carbamazepine (CBZ) monotherapy for epilepsy. She developed generalized clonic convulsions at the age of 7 years and 8 months. Treatment with CBZ was begun. Two months later she was admitted to our hospital because of severe anemia. Bone marrow examination revealed the almost complete absence of erythroblasts, with normal myelopoiesis and megakaryocytopoiesis, indicating pure red cell aplasia. Following the discontinuation of CBZ, she developed brisk reticulocytosis within 1 week and her hemoglobin level rose to a normal one within 1 month. Although the hematological toxicity of CBZ is well documented, isolated cessation of red cell production is uncommon. A patient who is undergoing treatment with CBZ should be carefully monitored, especially for serious adverse reactions including pure red cell aplasia.

Aicardi syndrome associated with an embryonal carcinoma

A Japanese girl is reported who had the typical clinical features of Aicardi syndrome associated with embryonal carcinoma. She developed infantile spasms at approximately 4 weeks of age; her seizures were intractable in spite of treatment with numerous antiepileptic drugs and ACTH. At 22 months of age, her left cheek gradually became swollen. Laboratory findings were normal except for a marked increase in serum alpha-fetoprotein. A transoral biopsy of the tumor revealed an embryonal carcinoma. This patient is the first reported with Aicardi syndrome and embryonal carcinoma. The relationship between congenital malformations and neoplasms is discussed.

Antiepileptic effects of Clobazam in children

Many benzodiazepines used as anticonvulsants have nitrogen radicals in positions 1 and 4. Clobazam has nitrogen radicals in positions 1 and 5. We studied the antiepileptic effect of clobazam in 36 patients with intractable epilepsies in childhood. Their ages were 1 year 1 month to 16 years 5 months (mean 8 years). The mean initial dose was 0.33 mg/kg of daily doses and increased up to 0.71 mg/kg. Nine cases (primary generalized epilepsy 2/2, secondary generalized epilepsy 7/29) were completely free from seizures, and another 9 (secondary generalized epilepsy 8/29, partial epilepsy 1/5) experienced a decrease of 50% or more in seizure frequency. Seizure frequency did not change in 16, and increased in the other 2 (secondary generalized epilepsy 2/29). The antiepileptic effects were observed on the first day to 10th day after clobazam treatment. There were recurrences of seizures in 4 out of 9 patients with complete control of seizures, 1 month alter in 3 and 10 months later in one. Mean serum clobazam level of 7 improved cases was 73 ng/ml and that of 3 cases with no response was 94 ng/ml. Although mild clinical side effects such as drowsiness were observed transiently in 17 cases, no abnormality was found in laboratory investigations performed.

Serial IMP-SPECT and EEG studies in an infant with hemimegalencephaly

An 8-month-old girl of hypomelanosis of Ito associated with hemimegalencephaly had frequent seizures beginning 44 h after birth. The seizures were secondarily generalized or unilateral initially, followed by infantile spasms at about 1.5 months of age. Frequent partial seizures appeared at 4 months of age. [123I]N-Isopropyl-p-iodoamphetamine (IMP) single photon emission computed tomography (SPECT) was performed serially during an interictal period at 1, 3 and 7 months of age. At 1 and 3 months, IMP-SPECT showed a marked increase of IMP uptake in the pathological left hemisphere and electroencephalography (EEG) revealed left-sided dominant hypsarrhythmia. At 7 months of age, a reversal was seen, there being decreased uptake on SPECT in the pathological hemisphere and abundant high amplitude background activity mingled with epileptic discharges on EEG in the non-pathological hemisphere. These serial changes of IMP uptake on SPECT seemed to reflect either changes in epileptic activity or maturational changes in cerebral perfusion in hemimegalencephaly.

EEG and CT abnormalities in xeroderma pigmentosum

ABSTRACT Xeroderma pigmentosum associated with neurological abnormalities is a less familiar neurocutaneous disorder. In this report, 35 patients with group A xeroderma pigmentosum were assessed for neurological complications. Of these, 17 showed microcephaly and 24 mental retardation. Of 25 patients over 7 years of age, 22 had sensorineural deafness and 12 showed spinocerebellar signs such as nystagmus, dysarthria, tremor and ataxia, while none below 7 years of age had such neurological complications. Thirty‐five EEG studies were performed on 29 patients, and 15 showed intermittent spindles of grouped theta waves with abnormal slow background activity and a poorly developed alpha rhythm, suggesting immature brain development or a regression from normal brain function in many areas including the diencephalon. Twenty‐six patients were examined by cranial CT scan, of whom 20 showed abnormal CT findings such as ventricular dilatation, diffuse cortical atrophy, and marked thickening of the calvarial bones. The incidence of abnormal EEG and CT findings increased with advancing age in accordance with the development of neurological complications in the CNS, thus suggesting a chronic progressive degenerative disease.

[3H]Zonisamide– Binding in Rat Brain

We previously reported that zonisamide inhibits both [3H]flunitrazepam and [3H]muscimol binding in rat brain. In the present study, [3H]zonisamide was found to bind in a saturable fashion to the crude synaptosomal fraction of whole rat brain. Linear regression analysis of the binding data in the Scatchard plot indicated a Kd of 90 nM, and a maximal binding capacity of 1.40 x 10(3) fmol/mg protein. Displacement studies revealed an inhibitory effect of clonazepam and an enhancement effect of GABA on specific [3H]zonisamide binding. These results suggest that specific [3H]zonisamide binding sites may have a tight correlationship with benzodiazepine receptors in rat brain.

Induced microseizures in West syndrome

Induced microseizures (IMS) were observed in a 5-month-old girl with symptomatic West syndrome. The seizures occurred following the suppression of infantile spasms with adrenocorticotropic hormone therapy and disappeared following the cessation of clonazepam administration. The ictal manifestations consisted of periods of irregular respiration, and respiratory arrest lasting for several seconds which often involved opening of the eyes and mild extension of the neck corresponding with the diffuse fast wave bursts in EEG activity observed during sleep. These seizures were thought to be equivalent to the IMS in Lennox-Gastaut syndrome, which have never been reported before in patients with West syndrome.