A dataset of neonatal EEG recordings with seizure annotations.

Neonatal seizures are a common emergency in the neonatal intensive care unit (NICU). There are many questions yet to be answered regarding the temporal/spatial characteristics of seizures from different pathologies, response to medication, effects on neurodevelopment and optimal detection. The dataset presented in this descriptor contains EEG recordings from human neonates, the visual interpretation of the EEG by the human experts, supporting clinical data and codes to assist access. Multi-channel EEG was recorded from 79 term neonates admitted to the NICU at the Helsinki University Hospital. The median recording duration was 74 min (IQR: 64 to 96 min). The presence of seizures in the EEGs was annotated independently by three experts. An average of 460 seizures were annotated per expert in the dataset; 39 neonates had seizures and 22 were seizure free, by consensus. The dataset can be used as a reference set of neonatal seizures, in studies of inter-observer agreement and for the development of automated methods of seizure detection and other EEG analyses.

Somatosensory and auditory processing in opioid-exposed newborns with neonatal abstinence syndrome: a magnetoencephalographic approach.

OBJECTIVE: Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems. METHODS: We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength and location of SEFs or AEFs were recorded. RESULTS: AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns. CONCLUSIONS: Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.

Magnetoencephalography in neonatology.

Magnetoencephalography (MEG) is a noninvasive method to study brain activity. In the previous decade the advantages of MEG -- good temporal resolution combined with good spatial resolution allowing separation of activated brain areas -- have been successfully used in gaining new information about the neonatal brain functioning. In this review, we discuss the findings from studies of spontaneous magnetoencephalogram and evoked responses to somatosensory, auditory, and visual stimulation. Our group has shown that stimulation of the upper limb in neonates evokes a response sequence reflecting activation of both primary (S(I)) and secondary somatosensory (S(II)) cortices. Like in mature brains, the earliest cortical response to median nerve stimulation reflects the arrival of afferent information to S(I). However, source modeling of the subsequent activation from S(I)suggests immature cortical functioning in neonates. Another feature typical for neonates is that the S(II)response is prominent in quiet sleep, unlike in adults in whom it diminishes in sleep. Interestingly, in very prematurely-born infants, we found alterations of the somatosensory responses at both group and individual levels. MEG provides a novel way to look at brain activity in neonates and can be used to increase knowledge of the development of brain processing and its disturbances.

Thalami and corona radiata in juvenile NCL (CLN3): a voxel-based morphometric study.

Juvenile neuronal ceroid lipofuscinosis (CLN3) is characterized by progressive cerebral atrophy. The purpose of this study was to re-evaluate the three-dimensional magnetic resonance (3D-MR) images of patients with CLN3 using voxel-based morphometry (VBM) to achieve a detailed understanding of the affected brain regions. T1-weighted 3D-MR images of 15 patients with CLN3 (age range: 12-25 years, mean age 17.6 years) and 15 age- and sex-matched controls were analyzed using VBM. VBM showed strikingly focal alterations in the brains of CLN3 patients: the gray matter volume was significantly decreased in the dorsomedial part of the thalami of CLN3 patients. In addition, the volume of the white matter was significantly decreased in the corona radiata, containing cortical efferents and afferents in the transition between the internal capsule and the subcortical white matter. These data suggest that the dorsomedial part of the thalamus and the corona radiata may have a central, previously unrecognized role in the pathogenesis of CLN3.

Trigeminal somatosensory evoked magnetic fields to tactile stimulation.

OBJECTIVE: To characterise the activation of the contra- and ipsilateral primary somatosensory cortex (SI) after tactile stimulation of the face. METHODS: Trigeminal somatosensory evoked magnetic fields (TSEFs) were recorded after tactile stimulation of the lower lip, cheek, chin and forehead in 11 healthy subjects. The responses were determined visually from the waveforms and modelled with equivalent current dipoles (ECDs). RESULTS: Contralateral SI responses were evoked in all subjects after lip stimulation, and in 91% and 64% after right and left cheek, 73% and 82% after chin and 64% and 27% after forehead stimulation. The responses usually showed an early double-peak wave pattern, the underlying sources localising to the SI. In addition, altogether 37 ipsilateral SI responses were evoked in eight subjects. Fourteen of these responses were amenable to ECD modelling and localised to ipsilateral SI. CONCLUSIONS: Tactile stimulation of the lip area reliably activates the contralateral SI in normal subjects, but the success rate for other trigeminal areas is lower. Ipsilateral responses can be present after stimulation of any of the trigeminal branches in normal subjects. SIGNIFICANCE: Recording of TSEFs after tactile stimulation of particularly the lip area provides a non-invasive technique to study the function of the trigeminal nerve.

Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients with ocular albinism with a novel mutation in the OA1 gene.

AIM: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. METHODS: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. RESULTS: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. CONCLUSIONS: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Auditory evoked magnetic fields to speech stimuli in newborns--effect of sleep stages.

The aim of the study was to examine whether a newborn can detect changes in a speech stimulus consisting of a fricative followed by a vowel /su/. In addition, we studied possible effect of the two sleep stages (active and quiet sleep) on the evoked magnetic responses. In young children (6 years), the same stimulus evokes a prominent deflection, consisting of two peaks. The first one (P1m) is evoked by the beginning of the fricative consonant and has a latency of about 145 ms. The second peak (P2m) with a latency of 340 ms, is evoked by the switch to the vowel. In newborns (n = 10), the waveform resembled that of the older children but latencies of the corresponding peaks were longer, 190 and 435 ms, correspondingly. The results suggest that already the newborn brain detects the change inside the auditory speech stimulus, namely the fricative sound changing into a vowel. However, the immaturity of the brain is reflected in the prolonged latencies. In addition, the responses were higher in amplitude in quiet sleep than in active sleep (F (1.9) = 36.5; p < 0.0002). This is in line with the enhanced somatosensory magnetic fields to tactile stimulation in quiet compared to active sleep in newborns.

Northern epilepsy syndrome (NES, CLN8)--MRI and electrophysiological studies.

Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental retardation, CLN8), an inherited childhood-onset epilepsy with mental retardation, has been recently characterized to belong to the family of neuronal ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years) with NES and eight healthy controls underwent magnetic resonance imaging (MRI) and electrophysiological evaluation with somatosensory evoked magnetic field (SEF) studies. The findings in NES were compared with the known findings in juvenile NCL (JNCL, CLN3) and Finnish variant late infantile NCL (vLINCLFIN, CLN5) that manifest around the same age as NES. Also postmortem MRI was performed on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all patients, whereas only two patients had slightly enlarged cerebral sulci. None of the MRIs demonstrated signal intensity abnormalities that are commonly seen in JNCL and vLINCLFIN and are considered to reflect the Wallerian degeneration after neuronal death. Generally SEFs in NES were within normal limits, indicating that the disease had not impaired the function of the neurons on the somatosensory pathway. In conclusion, MRI imaging and SEF findings suggest that the cerebral neuronal death and dysfunction in NES are minimal compared with JNCL and vLINCLFIN.

Neuronal ceroid lipofuscinoses in childhood.

NCL disorders are progressive brain diseases with an autosomal recessive inheritance in all eleven childhood types. These occur world-wide but may be enriched in some countries. In Finland altogether about 400 patients have been diagnosed during the last forty years. The most common types are the infantile and classic juvenile forms with an incidence of 1: 20,000 and 1: 21,000, respectively Personally followed-up are patients with infantile, classic and Finnish variant late infantile and classic juvenile types. Clinical, neurophysiological and neuroimaging findings in these four NCL forms are reviewed including also management and diagnostic aspects.

Phenotype-genotype correlation in eight patients with Finnish variant late infantile NCL (CLN5).

The authors analyzed the clinical phenotype, including MRI, of eight patients with Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCLFin; CLN5; MIM256731). Although the four known mutations, including one novel mutation identified in this study, have very different consequences for the predicted polypeptide, none of them results in an atypical phenotype, as has been reported in other forms of NCL. Thus, it seems likely that each mutation severely disturbs the normal function of the CLN5 protein.

Activation of multiple cortical areas in response to somatosensory stimulation: combined magnetoencephalographic and functional magnetic resonance imaging.

We combined information from functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to assess which cortical areas and in which temporal order show macroscopic activation after right median nerve stimulation. Five healthy subjects were studied with the two imaging modalities, which both revealed significant activation in the contra- and ipsilateral primary somatosensory cortex (SI), the contra- and ipsilateral opercular areas, the walls of the contralateral postcentral sulcus (PoCS), and the contralateral supplementary motor area (SMA). In fMRI, two separate foci of activation in the opercular cortex were discerned, one posteriorly in the parietal operculum (PO), and one anteriorly near the insula or frontal operculum (anterior operculum, AO). The activation sites from fMRI were used to constrain the solution of the inverse problem of MEG, which allowed us to construct a model of the temporal sequence of activation of the different sites. According to this model, the mean onset latency for significant activation at the contralateral SI was 20 msec (range, 17-22 msec), followed by activation of PoCS at 23 msec (range, 21-25 msec). The contralateral PO was activated at 26 msec (range, 19-32 msec) and AO at 33 msec (range, 22-51 msec). The contralateral SMA became active at 36 msec (range, 24-48 msec). The ipsilateral SI, PO, and AO became activated at 54-67 msec. We conclude that fMRI provides a useful means to constrain the inverse problem of MEG, allowing the construction of spatiotemporal models of cortical activation, which may have significant implications for the understanding of cortical network functioning.

Delayed classic and protracted phenotypes of compound heterozygous juvenile neuronal ceroid lipofuscinosis.

OBJECTIVE: To correlate the phenotypes with the genotypes of 10 Finnish juvenile neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) patients who all are compound heterozygotes for the major 1.02-kb deletion in the CLN3 gene. METHODS: The mutations on the non-1.02-kb deletion chromosomes were screened in 6 patients; in the other 4 patients the mutations were known (one affecting a splice site, two missense mutations, and one deletion of exons 10 through 13). Clinical features were examined, and MRI, MRS, somatosensory evoked magnetic field (SEF), and overnight polysomnography (PSG) studies were performed. RESULTS: A novel deletion of exons 10 through 13 was found in 6 patients belonging to three families. In the patients carrying the deletions of exons 10 through 13 the clinical course of the disease was fairly similar. Variation was greatest in the time course to blindness. In these patients the mental and motor decline was slower than in classic JNCL, but more severe than in the two patients with missense mutations in exons 11 and 13. MRI showed brain atrophy in 4 patients. One patient had hyperintense periventricular white matter, otherwise brain signal intensities were normal. SEFs were enhanced in patients older than 14 years, whereas in PSG all but the youngest 6-year-old patient showed epileptiform activity in slow-wave sleep. CONCLUSIONS: JNCL can manifest as at least three different phenotypes: classic, delayed classic, and protracted JNCL with predominantly ocular symptoms. Finnish compound heterozygotes have the delayed classic or the protracted form of JNCL.

Bone marrow transplantation in aspartylglucosaminuria--histopathological and MRI study.

This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.

Somatosensory evoked magnetic fields from primary sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis.

The present study evaluated neurophysiologic function of the primary sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis. A 122-channel magnetometer, which allowed studies of the somatosensory system in millimeter and millisecond precision, was used to record somatosensory evoked magnetic fields to median nerve stimulation from 10 patients and their matched control subjects. In both patients and controls, the somatosensory evoked magnetic fields from primary sensorimotor area typically consisted of N20m, P35m, and P60m deflections. In the patients, N20m was significantly delayed, whereas P35m peaked earlier than in the control subjects. The source strengths for N20m and P35m were greater in the patients than in the controls. Both deflections showed a significant positive correlation with the disease duration: the sources were stronger in the older patients than in the younger ones. P60m deflections were normal or reduced in the patients. The results indicated increased thalamocortical excitability in the sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis.

Aspartylglucosaminuria: radiologic course of the disease with histopathologic correlation.

Twelve living patients (aged 19 months to 32 years) with aspartylglucosaminuria were examined by magnetic resonance imaging (MRI), and the magnetic resonance (MR) images of 16 health volunteers (aged 4 to 32 years) were used as controls. One patient was examined twice. Postmortem MRI and histopathologic analysis were done on the brains of four additional adult patients. Signal intensities determined quantitatively on T2-weighted images differed significantly between patients and controls, being higher from the white matter (P < .0002) and lower from the thalami (P < .03) in the patients. The generally increased signal intensity of the white matter was most obvious in the young patients, with many focal areas of very high signal intensity in the subcortical white matter. The subcortical white matter showed a somewhat increased signal intensity even at the age of 32 years. In two of the four postmortem MR images, the distinction between the gray and white matter was still poor. At histopathologic analysis, the basic cortical cytoarchitecture was generally preserved but most neurons contained vacuoles, which were also found in the neurons of the deep gray matter. In two of the four autopsy cases the white matter showed diffuse pallor of myelin staining and some gliosis. Thus aspartylglucosaminuria is primarily a gray-matter disease also affecting white matter by delaying myelination.