Central motor reorganization in cerebral palsy patients with bilateral cerebral lesions.

Transcranial magnetic stimulation (TMS) has been used to describe cortical plasticity after unilateral cerebral lesions. The objective of this study was to find out whether cortical plasticity occurs after bilateral cerebral lesions. We investigated central motor reorganization for the arm and leg muscles in cerebral palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and 10 normal subjects, were studied. On CT/MRI, bilateral periventricular leukomalacia was observed in all spastic patients with preterm birth. In two normal subjects, motor responses were induced in the ipsilateral tibialis anterior, but no responses were induced in any normal subject in the ipsilateral abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were more common among CP patients, especially in TMS of the less damaged hemisphere in patients with marked asymmetries in brain damage: in 3 abductor pollicis brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites of highest excitability demonstrated that the abductor pollicis brevis and BB sites in CP patients were nearly identical to those of the normal subjects. In patients with spastic CP born prematurely, a significant lateral shift was found for the excitability sites for the tibialis anterior. No similar lateral shift was observed in the other CP patients. These findings suggest that ipsilateral motor pathways are reinforced in both spastic and athetoid CP patients, and that a lateral shift of the motor cortical area for the leg muscle may occur in spastic CP patients with preterm birth.

Excitability recovery curves of blink reflexes in patients with athetotic cerebral palsy.

We evaluated the brainstem function or its excitability by the blink reflex evoked with the electrical stimulation to the supraorbital nerve in 10 patients with athetotic cerebral palsy compared with 10 normal subjects and 7 spastic type patients. There were no differences in stimulus intensity, latency of R1 and R2 components, and duration and area of EMG activity of the R2 component of the blink reflex elicited by single stimulation among the two patients' groups and normal subjects. R1 recovery cycle to paired stimuli in the athetotic group showed a facilitation of the test responses by the conditioning stimuli at 100 and 200 ms intervals, but were not significantly different from those in the normals. On the other hand, the R2 recovery curve in the athetotic group showed a significant hyperexcitability at all intervals from 100 to 600 ms compared to the normals. Our results from the R2 hyperexcitable recovery to paired stimuli are indicative of increased brainstem interneuronal excitability in athetotic patients and similar to the results reported in the disorders of the basal ganglia, i.e. Parkinson's disease, dystonia and blepharospasm. We suggest that this hyperexcitability might be caused by abnormal input possibly from the basal ganglia upon these brainstem interneurons.

Normalization of creatine kinase level during arthritis in a patient with Becker muscular dystrophy.

A patient with Becker muscular dystrophy had transient arthritis. During the active illness his serum creatine kinase (CK) level normalized and serum levels of soluble interleukin 2 (IL-2) receptor, IL-6, IL-1 receptor antagonist, and soluble tumor necrosis factor receptor 2 were elevated. CK increased to his usual levels after arthritis remission whereas the levels of inflammatory cytokines and their inhibitors decreased.

[Hyperexcitability of the blink reflex in a child with opsoclonus-myoclonus syndrome].

A 13-month-old girl developed opsoclonus-myoclonus syndrome in association with neuroblastoma. She showed irritability, hyperhidrosis and a bad temper. Serum and urinary vanilmandelic acid, homovanilic acid and catecholamines were elevated at the same time. Chest CT demonstrated the presence of neuroblastoma in the paravertebral region. Cranial CT and MRI revealed no abnormal findings. Brainstem auditory-evoked potentials and short latency somatosensory evoked potentials were normal, whereas blink reflex showed long duration and high amplitude of late components (R2 and R2') indicating hyperexcitability of the interneurons in the lower brainstem. These findings improved gradually as opsoclonus disappeared. Her neurologic symptoms resolved completely within 2 years after the resection of the tumor. The hyperexcitability of the blink reflex may indicate the hyperactivity of the neurons in the brainstem reticular formation responsible for the abnormal saccadic eye movements (opsoclonus), which could be caused by the oversecretion of dopamine or by the supersensitivity of dopaminergic receptors.

[A case of learning-disabled child with a white matter lesion in the left parietal lobe].

We reported a learning-disabled boy, 7-year-old and right handedness, who was similar to developmental Gerstmann syndrome. Dyscalcuria, right-left disorientation, dysgraphia and finger agnosia were correlated with his sequential disorder which was clearly presented by Kaufman Assessment Battery for Children. In this case, a small infarcted lesion was found in the white matter near the left semioval center on MRI. Hypoperfusion of left parietal lobe was also detected by SPECT. The hemisphere dominant in language was assumed to be on the left side by dichotic listening test. We suggested that left parietal lesion was associated with his higher cortical dysfunction.

Pontine hypoplasia in a child with sensorineural deafness.

A 2-year-old girl with bilateral sensorineural deafness showed pontine hypoplasia as well as a bulging contour of the pontine tegmentum on magnetic resonance imaging (MRI). There were no bilateral responses of brainstem auditory-evoked potentials (BAEPs). The absent late components of blink reflex (BR) indicated brainstem dysfunction. Chromosomal abnormalities and neurodegenerative or neurometabolic disorders, which might have been the cause of the pontine hypoplasia, were ruled out. The authors describe a rare case with pontine hypoplasia combined with sensorineural deafness and absent blink reflex and suggest that the brainstem in this child may become involved in the early gestation period.

Mechanisms of central motor reorganization in pediatric hemiplegic patients.

Twenty hemiplegic patients were studied with transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) of the biceps brachii (BB) and the abductor pollicis brevis muscles (APB) were recorded on both sides simultaneously. TMS was carried out with an 8-shaped coil over different scalp positions in the intact hemisphere. Bilateral MEPs of BB were elicited in patients with later childhood lesions as well as early lesion, but those of APB were only elicited in the latter (up to 2 years). In patients with prenatal or birth lesion on BB and in all patients on APB, cortical maps of MEP amplitude of paretic and non-paretic sides showed similar distributions. There were no remarkable differences in mean latency between both sides, and correlation coefficients of MEP amplitude between both sides were high in these patients. In patients with postnatal lesion on BB, MEP maps of both sides showed different distributions, ipsilateral MEP latencies were delayed and correlation coefficients were low. We suspect that ipsilateral MEPs after early lesion derive from axonal sprouting both in the proximal and the distal muscles. After postnatal lesion, other mechanisms of ipsilateral motor projection take place in the proximal muscles, but not in the distal ones.

IgA and IgG2 deficiency associated with zonisamide therapy: a case report.

PURPOSE: To report a previously undescribed adverse effect, IgA/IgG subclass deficiency associated with zonisamide (ZNS) therapy. METHODS: Serum IgA and IgG subclass levels were determined by the turbidimetric immunoassay and enzyme-linked immunosorbent assay, respectively, in a 2-year-old boy with postmeningitis sequelae who was treated by ZNS. RESULTS: Four months after initiation of ZNS, combined deficiency of IgA and IgG2 was noted. After cessation of ZNS, serum IgA level was promptly increased. IgG2 level was gradually increased, but remained subnormal after 7 months. CONCLUSIONS: This case documents, for the first time, the action of ZNS on IgG immune system as well as IgA system. If patients with ZNS therapy showed IgA deficiency and recurrent infections, it is preferable to check serum IgG subclass concentrations as well.

Magnetic stimulation of the lumbosacral vertebral column in children: normal values and possible sites of stimulation.

We describe a technique of lumbosacral magnetic stimulation (MS) using an 8-shaped coil in 44 normal children and 7 normal adults on the lower limb muscles. In most child subjects and some adult subjects, we observed two peaks in amplitude of the motor evoked potential (MEP) following MS when the coil was moved caudally from Th8 to S2. The rostral peaks of MEP were elicited at L1/2, and the caudal peaks were elicited below L3. Rostral peak amplitudes were considerably higher in younger children than in adolescents and adults. MEP latencies tended to decrease as the coil was moved from Th11 to L4/5, and were almost constant at caudal to L4/5 in most child subjects, especially in younger children. Comparison of MEP latencies with the peripheral motor conduction times by the F technique suggests that the proximal sites of excitation of the nerve root are 0.0-0.6 ms conduction times distal to the motoneuron, while the distal sites of excitation are 2.1-2.9 ms conduction times distal to the motoneuron. We conclude that performing MS using the 8-shaped coil enables us to excite the nerve roots near the motoneuron as well as those near the intervertebral foramen, and that MEPs are elicited more easily in younger children than in adolescents and adults.

Facilitation of ipsilateral motor pathways during recovery from hemiplegia in two adolescent patients.

In two hemiplegic patients with acquired cerebral lesions, transcranial magnetic stimulation (TMS) was carried out to examine the contribution of the ipsilateral motor pathways to recovery from hemiplegia. A 13-year-old girl (patient 1) had acute hemiplegia due to a rupture of an arteriovenous malformation, and a 13-year-old boy (patient 2) had subacute hemiplegia due to a brain tumour. They showed complete upper limb palsy but recovered after therapy; patient 1 had slightly disabled motor function of the arm, and patient 2 recovered completely. Motor evoked potentials (MEPs) were recorded from the biceps brachii muscles on both sides. The MEPs of the paretic biceps were only elicited by TMS of the intact hemisphere at the beginning of recovery from hemiplegia, but not by TMS of the affected hemisphere. The MEP amplitudes increased and cortical representation areas for the paretic biceps by TMS were enlarged temporarily during recovery. They regressed in patient 1 and MEPs were not evoked at all in patient 2 after recovery. Conversely, MEPs were obtained by TMS of the affected hemisphere after recovery in both patients. These data indicate that ipsilateral motor pathways play a role in recovery from hemiplegia, especially at the beginning, and become inactivated when the contralateral motor pathways recover.

[Computed tomography and magnetic resonance imaging of the brain in congenital rubella syndrome].

Nine children with congenital rubella syndrome were examined with respect to the relation between clinical symptoms and the findings of computed tomography (CT, 9/9 cases) and magnetic resonance imaging (MRI, 7/9 cases). All patients had deafness, and three had relatively severe sequelae in the central nervous system (CNS), such as mental retardation (MR), cerebral palsy (CP) or microcephaly. In four patients, dilatation of the lateral ventricles was found by CT; in four patients, low-density areas were noted in the periventricular white matter and/or the subcortical white matter; one patient showed a spotty calcified area in the lenticula. No abnormal findings were found by CT in other three patients. MRI in seven children demonstrated areas of prolonged T1 and T2 relaxation times in the white matter in all of them. In relation to clinical symptoms, five patients without dilatation of the lateral ventricles had no sequelae except deafness. On the other hand, in four patients with dilation of the lateral ventricles, three had MR, CP or microcephaly. This study showed that there was a close relation between the ventricular dilatation and sequelae with in CNS, whereas abnormal intensity areas in the white matter found by MRI were not related well to the sequelae of CNS.

[The blink reflex in severely handicapped patients with dysphagia].

We investigated the blink reflex in 27 severely handicapped patients. 15 males and 12 females, from 5 to 60 years old. They were divided into three groups; the tube-feeding group (9 patients), the oral-feeding group (9 patients), and the mixed-feeding group (9 patients). Seven normal subjects also were included in this study. There was a significant difference in the late ipsilateral component (R2) between the tube-feeding and oral-feeding groups. The average R 2 time were 43.0 msec. in the tube-feeding group and 36.7 msec. in the oral feeding group. The auditory brainstem response (ABR) showed no significant difference between the two groups. These results suggested that the swallowing function in the patients needed for tube feeding was affected by not only the cortical lesions but also the brainstem ones. Furthermore, it is speculated that the degree of brainstem dysfunction in the tube-feeding group was more severe than in the non-tube-feeding group. The blink reflex is one of the useful electrophysiological parameters for evaluating the brainstem function in severely handicapped patients with dysphagia.

Epidemiological and genetic studies of Huntington's disease in the San-in area of Japan.

After the DNA diagnosis, we evaluated the prevalence of Huntington's disease (HD) in the San-in area of Japan, and confirmed the founder effect. There were 10 patients with HD in the San-in area, who were diagnosed clinically. The expansion of the CAG repeat was observed in 9 patients with HD members in their families, although those family members of the patients had already died. In the patient who had no positive family history, expansion of the CAG repeat was not seen. The prevalence of HD was 065/100,000 in this area. The common haplotype studied by the polymorphism marker of D4S136 was shown in all 9 HD patients, although they were observed in only 2.7% of the normal population. These results suggested a common ancestor of these HD patients.

[Prevalence and founder effect of Huntington's disease in the San-in area of Japan].

After the DNA diagnosis, we evaluated the prevalence of Huntington's disease (HD) in the San-in area of Japan, and confirmed the founder effect. The population of the area was 1,387,000 on October 1st, 1993. There were 10 patients with HD in the San-in area, who were diagnosed clinically. They all had involuntary movement, mental disturbance, changes of character and atrophy of the caudate nucleus. However, one of the patients showed no positive family history of HD. The other nine patients had members with HD in their families, although those family members of the patients had already died. The expansion of the CAG repeat was observed in nine of the patients. In the patient who had no positive family history, expansion of the CAG repeat was not seen. According to the nine patients with expansion of the CAG repeat, the prevalence was 0.65/100,000. Haplotypes using polymorphism markers of D4S111 and D4 S136 were studied. The haplotypes which were observed in only 2.7% of the normal population were shown in all nine HD patients. Thus, the obvious disequilibrium was seen. These results suggested a common ancestor of these HD patients.

[Taste disturbance as an initial manifestation of Guillain-Barré syndrome in a 14-year-old girl].

We reported a 14-year-old girl who showed taste disturbance as an initial manifestation of Guillain-Barré syndrome (GBS). After an upper respiratory infection, she initially complained of taste disturbance, diplopia and salivation, followed by weakness in the legs and numbness in the extremities. On admission, she showed taste deficiency for sweet and sour sense, and a decline of salty and bitter taste. Weakness in the legs and disappearance of deep tendon reflexes were also noticed. We considered that the findings of electrophysiological examinations would conform to demyelinating features. Laboratory examinations revealed an increase of memory T cells in the peripheral blood and an elevated level of myelin basic protein in the cerebrospinal fluid. Based on clinical features and laboratory data, the diagnosis of GBS was made. We should keep taste disturbance in mind as one of the signs of GBS.

[Short somatosensory evoked potentials in patients with Fukuyama type congenital muscular dystrophy--a comparison with CT and MRI findings].

Seven patients with Fukuyama type congenital muscular dystrophy were studied. Low density areas (LDs) in the cerebral white matter on cranial CT were present in all 4 patients younger than 13 years of age and in 1 of 3 adult patients. LDs corresponded to low signals on T1 weighted MRI image and high signals on T2 weighted MRI image. The follow-up MRI showed a decreased tendency of the abnormal signals in 2 patients. Short somatosensory evoked potentials (SSEPs) in two infants, aged 4 months and 8 months, showed absent or depressed N1 amplitudes and delayed interpeak latencies from P3 to N1. N1 amplitudes increased on follow-up studies. SSEPs of five patients, who were older than 2 years of age, showed normal N1-P3 latencies. Amplitude of N1 was low in 2 patients with LD. Since the absent or depressed amplitude and delayed latency of N1 improved with the decrease of abnormal signals on MRI, we considered that N1 abnormalities show delayed myelination.

Non-radioactive DNA diagnosis for the fragile X syndrome in mentally retarded Japanese males.

A rapid screening test was developed to detect CGG repeat expansion of the FMR-1 gene causing the fragile X syndrome by a non-radioisotope PCR technique. A biotin-labeled primer was initially used and the biotin-labeled PCR product was detected by means of chemiluminescence. The normal PCR product of around 300 bp was not created in the abnormal FMR-1 gene sample with this method. Four positive samples were found among those from 226 mentally retarded males, but the CGG repeat expansion was shown on Southern blot analysis in only one sample. To eliminate false-positive samples, a hybridization method involving a biotin-labeled (CGG)s oligonucleotide was developed for the PCR product and the CGG repeat expansion could be detected. Finally, 256 mentally retarded males in Japan were examined and only 2 abnormal samples were detected. The prevalence of this abnormality was less than 1%, which is relatively lower than those reported previously.

Effect of antiepileptic drugs on thyroid function.

Chronic treatment with antiepileptic drugs (AED) is known to reduce serum thyroid hormone levels. Serum thyrotropin (TSH) level is unchanged despite low thyroxine (T4) level. We studied serum tri-iodothyronine (T3), T4 and TSH in 30 epileptic patients prior to discontinuation and 2, 4, 8 and 16 weeks after AED discontinuation. One AED was discontinued in each patient. Serum T3 levels were reduced consistently after AED discontinuation. Serum T4 and rT3 levels were increased, but not persistently. Serum TSH levels were unchanged. Our results suggest that during AED treatment serum T3 level was increased. This could be an increased conversion of T4 to T3. An acceleration of thyroid hormones degradation by enzyme induction is physiologically balanced by an increased conversion of T4 to T3.

Carbamazepine-induced thrombocytopenia and carbamazepine-10,11-epoxide: a case report.

The case of a patient who developed thrombocytopenia during treatment with carbamazepine (CBZ) is described. The platelet count recovered soon after discontinuation of CBZ, Lymphocyte stimulation test with carbamazepine-10, 11-epoxide (CBZ-10, 11-EPOX), a major metabolite of CBZ, was positive, although with CBZ it was negative. These findings suggest that CBZ-10, 11-EPOX was possibly causative in the pathogenesis of CBZ-induced thrombocytopenia in this case.