Hypothalamic hamartoma with skeletal malformations, gelastic epilepsy and precocious puberty

A child is described who has skeletal malformations, gelastic epilepsy, precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on MRI. The precocious puberty has been successfully medically managed, though her seizures are difficult to control. The combination of all four features has not been described previously.     

Hypothalamic hamartomas and gelastic epilepsy: a spectroscopic study

BACKGROUND: Patients with hypothalamic hamartomas present with epileptic attacks of laughter and later experience multiple seizure types and cognitive decline, suggestive of secondary generalized epilepsy. It has been suggested in the past that gelastic seizures originate in the temporal lobes rather than in the hamartoma, but temporal resections have been ineffective. Recent electrophysiologic evidence suggests that the epileptogenic discharges may originate in the hamartoma itself. METHODS: We used proton magnetic resonance spectroscopic imaging to quantify the amount of neuronal damage in the temporal lobes and hamartomas of patients with hypothalamic hamartomas and gelastic seizures. Five patients were studied and the relative intensity of N-acetylaspartate to creatine (NAA/Cr) was determined for both temporal lobes as well as for the hamartoma. These values were compared with signals from the temporal lobes and hypothalami of normal control subjects. RESULTS: NAA/Cr was not significantly different from normal control subjects for either temporal lobe, nor was there a significant asymmetry between the two temporal lobes for any of the patients. NAA resonance signals were present in the hamartomas, and the ratio of NAA to Cr was decreased in the hamartomas compared with the hypothalami of normal control subjects (t = 4.5, p = 0.005). CONCLUSIONS: We found no detectable neuronal damage in the temporal lobes of patients with hypothalamic hamartomas and gelastic epilepsy. This is further evidence that gelastic seizures do not originate in the temporal lobes of these patients.     

Platelet glycoprotein Ia* is the processed form of multimerin--isolation and determination of N-terminal sequences of stored and released forms

The authors report on a patient who exhibited intractable epilepsy due to an inaccessible hypothalamic hamartoma and subsequently underwent stereotactic radiosurgery. This 25-year-old man had a 24-year history of intractable gelastic and tonic-clonic seizures. Magnetic resonance (MR) imaging performed at examination as well as that performed 30 months earlier demonstrated a nonenhancing and nonprogressive spherical mass, approximately 10 mm in diameter, located on the patient's right side at the floor of the third ventricle. Focal radiation treatment performed with a gamma knife unit administered 36 Gy to the center and 18 Gy to the periphery of the lesion. This treatment resulted in an improvement in seizure control. Before the patient underwent radiosurgery, he suffered from three to six generalized seizures per month in spite of attentive compliance with an anticonvulsant medication regimen. After irradiation of the harmatoma, the frequency of the seizures transiently increased and then subsided 3 months posttreatment. The patient has been free of seizures for the last 21 months, with no neurological or endocrinological complications. Magnetic resonance imaging performed 12 months posttreatment demonstrated complete disappearance of the lesion.     

The long-term course of spike and wave complexes in the waking EEG of chronic schizophrenics

Nineteen chronic schizophrenics (8 males and 11 females) showed at least one spike and wave complex (SpW) in their rested-awake EEGs during long-term neuroleptic treatment. The age at the first appearance of the SpW ranged from 16 to 60 years, and the duration of neuroleptic medication preceding its appearance was from 1 to 35 years. Two types of SpW waveform were discriminated; one was a diffuse high voltage isolated 3.5-4 Hz SpW complex, and the other a diffuse moderate voltage 5-6 Hz SpW burst. In EEG studies repeated over the long-term, the presence of SpW was transient in 11 cases, intermittent in 5 cases, and continuous in 3 cases. Three patients had generalized tonic-clonic clinical seizures; two of their EEGs did not show SpW until after the onset of seizures. All three responded well to adjunctive anticonvulsant therapy. The other 16 patients exhibited SpW but did not have clinical seizures with or without prophylactic use of anticonvulsants. The SpW in the EEG of chronic schizophrenics might be an indicator of predisposition for seizure, but it is not a good predictor of seizure.     

Paediatric pain management--the next step?

Congenital bilateral perisylvian syndrome (CBPS) is a recently described, neuronal migration disorder, characterized by pseudobulbar palsy, epilepsy and mental retardation and bilateral perisylvian dysplasia. A 15-year-old boy was diagnosed with CBPS according to the typical clinical, and magnetic resonance imaging (MRI) features. The patient was suffering from atypical absence seizures, repeating daily in spite of antiepileptic drug therapy, since age 7 years. He had also experienced rare generalized tonic-clonic seizures and complex partial seizures. Neurological examination showed severe restriction of tongue movements, severe dysarthria, dysphagia, facial diplegia, mild pyramidal signs and moderate mental retardation. A computed tomographic (CT) scan demonstrated bilateral perisylvian enlargement. The diagnosis was corrected with MRI after six years. Frequent irregular generalized spike and wave abnormalities and focal sharp and slow waves over the posterior regions of both hemispheres were shown by electroencephalograms (EEG). The patient was treated with Na-Valproate, carbamazepine and lamotrigine but did now show any significant change in seizure frequency in the eight-year follow-up period. Intractable seizures, mental retardation and particularly congenital pseudobulbar palsy suggest this congenital entity. Those patients who exhibit these typically clinical features, must have MRI.     

Case report: fibrolamellar hepatocellular carcinoma in a Japanese woman: a case report and review of Japanese cases

There have been few reports on cerebral arteriovenous malformation (AVM) of newborns. We present here an interesting case of occult AVM diagnosed 17 years after an episode of acute subdural hematoma in the neonatal period. The cause of subdural hematoma had remained unclear and the patient had suffered from an intractable epilepsy of 17 years duration. Seizures were mainly characterized by drop attacks and included other seizure types such as complex partial seizure and generalized tonic clonic seizure. The symptoms had gradually become worse and the intervals between the occurrences of symptoms had become shorter. An interictal scalp EEG showed a focal spike in the left temporoparietal lobe. CT and MRI of that region demonstrated a porencephalic cyst which was supposed to have resulted from an old hematoma. There were no vascular abnormalities in angiography. Temporoparietal craniotomy and a corticogram were performed. The cortex with a focus was resected and the disappearance of a focal spike in the corticogram was confirmed during operation. Microscopically the cortex included AVM with gliosis. The initial postoperative course was good and seizures disappeared immediately after the operation. However, the symptoms of drop attacks observed before operation began to occur again 3 months later. The fact of postoperative recurrence suggests that the long history of the patient's seizures originating from AVM may have produced secondary epileptic foci.     

Routine microbiological testing in sudden and unexpected infant death

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.     

Clinical picture of autoimmune hemolytic anemia

We describe a boy who has gelastic epilepsy, precocious puberty, hypothalamic hamartoma, and agenesis of the corpus callosum. We believe that this is the first documented case in which agenesis of the corpus callosum has been associated with hypothalamic hamartoma and gelastic epileptic syndrome in a child.     

Ictal oroalimentary automatisms with preserved consciousness: implications for the pathophysiology of automatisms and relevance to the international classification of seizures

A patient showing seizures presenting ictal automatisms with preserved consciousness is reported. A 30-year-old, right-handed man with normal development and without family history of epilepsy was referred for surgical treatment of epilepsy. At 15 he began to have seizures, starting with an epigastric aura, occasionally developing automatisms (lip-smacking, chewing), sometimes followed by tonic-clonic convulsions. At the time of referral, he averaged six convulsive seizures per year and one nonconvulsive per week. His sleep EEG showed sharpened slow activity over the right anterior quadrant magnetic resonance imaging (MRI) showed a benign lesion in the mesial aspect of the right occipital lobe. Simultaneous video monitoring and intracranial EEG with subdural strips recording from the right temporal and occipital lobes was undertaken. During one seizure, he had pronounced oroalimentary automatisms while holding a conversation with a technician, answering her questions, and explaining details of his seizures. Memory of this event was preserved. At seizure onset, spike activity was seen at the mesial occipital strips. At midseizure, high-voltage sharpened delta was seen throughout the right hemisphere. Left-sided scalp electrodes remained relatively uninvolved. The lesion, a dysembryoplastic neuroepithelial tumour was removed. Surgery was followed by abolition of seizures described. Because it is agreed that complex partial seizures require impaired consciousness, a history of automatisms with retained consciousness usually suggests nonepileptic attacks. This case suggests that automatisms in epileptic seizures can take place with minimal loss of consciousness, particularly if there is widespread but unilateral involvement. The need for a revision of the International Classification is suggested.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

Surgical management of intractable epilepsy in patients with ganglioglioma

Long-standing intractable seizures are common manifestation of cerebral gangliogliomas. There is much controversy regarding the most appropriate surgical treatment (lesionectomy vs resection of the epileptogenic cortex with the lesion) for patients with intractable epilepsy associated with gangliogliomas. We reported 2 cases, in which the favorable seizure outcome was obtained following lesionectomy alone. (Case 1) Nine-year-old female developed attack of abnormal sensation in her left upper limb followed by motor seizure in her left limbs since 5 years old. MRI revealed hyperintense tumor in the right medial frontal lobe. Chronic invasive subdural recording showed that ictal onset zone was located in the hand motor area. Following lesionectomy alone, she became free from seizures. (Case 2) Eight-year-old girl had intractable generalized seizure since 6 years old. MRI revealed a cystic tumor in the right parietal lobe. She had multiple spike foci on electroencephalography and magnetoencephalography, and intraoperative electrocorticography failed to reveal the paroxysm. Following lesionectomy, she had good relief with less than one minor seizure per 1-3 months. Thus, lesionectomy, even without resection of the epileptogenic cortex, may improve seizure outcome in patients with ganglioglioma-associated epilepsy.     

Electroencephalogram and clinical focalities in juvenile myoclonic epilepsy

Partial seizures and asymmetric abnormalities seen on electroencephalogram (EEG) are infrequent in juvenile myoclonic epilepsy, but when present, can lead to a misdiagnosis of partial seizures. We report four patients with juvenile myoclonic epilepsy who had generalized spike or polyspike and wave discharges on EEG in addition to clinical and EEG evidence of focality. The clinical course and response to therapy was similar to that in typical juvenile myoclonic epilepsy.     

Surgical treatment of epilepsy in tuberous sclerosis: strategies and results in 18 patients

BACKGROUND: Seizures in patients with tuberous sclerosis complex (TSC) are often intractable to antiepileptic medications and searching investigation may provide evidence that surgical treatment can be considered. OBJECTIVE: To review the results of investigation and surgical therapy, a treatment modality not generally considered in patients with medically refractory seizures and TSC. METHODS: We report 18 patients (9 male) with TSC who underwent surgical treatment of medically refractory epilepsy. Twelve patients had a well-localized epileptogenic lesion and were treated by lesionectomy or focal resection. Resections were: 7 frontal, 4 temporal, 1 frontotemporal, 1 occipital, and 1 frontoparietal. Four patients underwent more than one operation. Six patients had corpus callosotomy (CC). RESULTS: Follow-up ranged from 1 month to 47 years. Outcome of the patients treated by resection was excellent in 7 (5 were seizure-free and 2 had auras only), good in 1, fair in 3, and 1 was lost to follow-up. Best outcome was obtained in patients who had focal seizures and good imaging and EEG correlation, although they might have multiple seizure types, other imaging abnormalities, and multifocal or generalized EEG findings. When there was no such correlation, CC was found to be an option as five patients had at least some improvement and only one showed no change. CONCLUSION: Surgical treatment of patients with TSC and intractable epilepsy is most effective when a single tuber or epileptogenic area can be identified as the source of seizures and resected. This may be possible even when other tubers or diffuse EEG abnormalities are present. In patients with unlocalizable epileptic abnormalities, palliation may be obtained by CC.     

Index of suspicion. Case 1. Hypersensitivity pneumonitis

We report a case of a 17-year-old white girl with Marfan's syndrome and generalized absence-type seizures since 11 years of age. A video EEG recording for six hours demonstrated 52 episodes of clinical generalized absence-type seizures and three-per-second spike and wave epileptiform discharges, characteristic of petit mal epilepsy. Sodium valproate therapy was successful in controlling her seizures. In this article, we review various possible causes of epilepsy in patients with Marfan's syndrome.     

The choleretic effects of licorice: identification and determination of the pharmacologically active components of Glycyrrhiza glabra

The authors retrospectively reviewed ten pediatric brain tumor patients with intractable seizures who underwent lesionectomy without intentional identification and resection of the epileptogenic region to assess the clinical features and seizure outcome after lesionectomy in such patients. Seizures were complex partial in seven cases and simple partial, absence, and generalized tonic-clonic in one case each. Tumors were located at the medial temporal lobe in four cases, at the frontal lobe in four cases, at the parietooccipital and the suprasellar areas in one case each. The most common pathology was benign oligodendroglioma (five cases) followed by ganglioglioma (two cases). Others were pleomorphic xanthoastrocytoma, hamartoma, and primitive neuroectodermal tumor (one case each). In four cases, complete removal of the tumor was feasible. Postoperatively nine of the ten patients showed favorable seizure control (Engel's classification 1 and 2) and of these, six were seizure-free during the follow-up period (mean duration: 40 months). Therefore, lesionectomy can be an appropriate initial treatment for patients with brain tumor and medically intractable seizures.     

Variability in visual cortex activation during prolonged functional magnetic resonance imaging

OBJECTIVE: To review the EEG features of ring 20 syndrome in two patients and determine the characteristic pattern of this syndrome. The features of our cases and 24 patients reported in the literature will be discussed. SUBJECTS AND METHODS: Report of two patients and review of literature. RESULTS: The two patients had intractable epilepsy since childhood. Their clinical seizures were mostly complex partial seizures. Often the patients seizures were of prolonged duration. Ictal EEG revealed characteristic slow waves, and sharp waves. The slow waves were (1) usually synchronous high-voltage slow waves with or without a spike component predominantly in the frontal and frontopolar areas, (2) sometimes showed a change in frequency every several seconds, (3) continued for a long period, and (4) easily spread diffusely. The sharp waves were 5-6 Hz irregular and diffuse discontinuous sharp waves, and sometimes appeared predominantly in the centroparietal area. The clinical seizure pattern and EEG findings were similar in the 24 published cases. CONCLUSIONS: These EEG findings may be a characteristic feature of ring 20 syndrome and thus may be useful as a diagnostic clue.     

New trends in glass-ionomer chemistry

Carbamazepine (CBZ) is an effective anticonvulsant agent. Current literature reports describe several cases of seizure exacerbation and/or EEG worsening due to CBZ with a high prevalence in children and adolescents; we report 10 new cases. Nine patients had epilepsy; one showed delayed psychomotor development and frequent EEG paroxysmal abnormalities. Four patients were on monotherapy, six on polytherapy. All but one had therapeutic CBZ plasma concentrations. Seizures increased in frequency in nine, and in eight patients new seizure types appeared, mostly absences. Cognitive functions/behaviour worsened in eight; EEG recordings showed slowing background activity and increased paroxysmal abnormalities, in six cases diffuse/generalized spike waves were seen and in two continuous spike wave discharges. The mean time of clinical EEG worsening was 1-2 days after introduction of CBZ at therapeutic doses. After CBZ withdrawal clinical EEG improvement was evident in a few days. The underlying pathogenetic mechanism is not yet understood. However, the pathophysiology of seizure exacerbation might be related to the interaction between age-related alterations in the balance of excitation and inhibition in the developing thalamocortical circuitry and the essential activity of CBZ that tends to induce interictal discharges.     

Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings

Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.     

Electroencephalographic correlates of audiogenic seizures during ethanol withdrawal in mice

C57BL/6Bg mice had silver bead electrodes chronically implanted on the surface of the cortex and had their cortical EEG recorded during audiogenic seizures following ethanol withdrawal. For 7 days, the experimental groups were fed a liquid diet containing 6% v/v ethanol ad lib as the only source of food and water. The control group was fed a similar diet containing an isocaloric amount of sucrose. The cortical EEG's of experimental and control groups before, during, and after treatment were virtually identical. Only the experimental group was susceptible to audiogenic seizures. During audiogenic seizures, the cortical EEG showed no sign of spike waves or paroxysmal activity. This is in contrast to picrotoxin convulsions with these same mice as well as to spontaneous convulsions in animals following ethanol withdrawal. Similar EEG observations have been reported on audiogenic seizures from genetic and acoustically primed susceptibilities. Consequently, we suggest that all audiogenic seizure responses, including those during ethanol withdrawal, are a type of subcortical epilepsy.     

Surgical treatment for partial epilepsy among Norwegian children and adolescents

We conducted a retrospective longitudinal self-controlled study of 64 patients aged 4-19 years treated with resective surgery for partial epilepsy from 1952 to 1988. Approximately 60% of patients experienced > 95% reduction in seizure frequency, and 70% had worthwhile improvement of at least 75% reduction. Seizure relief was more frequent among patients who underwent operation after 1978, and significant differences by time period of operation were noted for those with temporal lobe excisions and patients with normal tissue histology. The region of resection and the age at treatment did not provide significant information with respect to seizure outcome. Postresection electrocorticography (ECoG) and EEG of the first postoperative year predicted later seizure outcome. Small neurologic deficits were more common among patients resected in the temporal lobe than in patients resected in the frontal lobe. Half of the patients with preoperative unilateral focal activity and a third of those with bilateral focal activity had normal EEG postoperatively. One fourth had discontinued antiepileptic drug (AED) therapy. As expected, long-term mortality was significantly higher than the mortality of the general population. Seven patients died during follow-up. Two male patients committed suicide.