Neuropsychiatric profile of paediatric hypothalamic hamartoma: systematic review and case series.

AIM: To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma. METHOD: We retrospectively analysed case notes for all individuals with hypothalamic hamartoma referred to Great Ormond Street Hospital, London, between 2000 and 2016. In addition, a systematic review aiming to identify all previous paediatric case series was performed. Psychiatric symptoms, demographics, physical comorbidities, and cognitive functioning were recorded for all cases where possible. Analyses were performed to determine which factors were associated with psychopathology and potential mechanisms investigated. RESULTS: Forty-six cases were included in the case series (28 males, 18 females; mean age at assessment 11y 8mo [1y 11mo-16y 11mo, SD 4y 0mo]). Twenty-nine papers representing data from 264 cases met inclusion criteria for the systematic review. Overall, at least 50% of cases presented with psychopathology. Epilepsy, intellectual disability, and male sex were associated with externalizing disorders (attention-deficit/hyperactivity disorder, conduct and oppositional defiance disorders, and rage attacks). Intellectual disability mediated the effects of epilepsy on externalizing psychopathology. No factors were associated with internalizing disorders (anxiety and depressive disorders), although these were not well reported. INTERPRETATION: Psychiatric comorbidities are highly prevalent in the presentation of paediatric hypothalamic hamartoma. The aetiology of psychopathology comprises a range of interacting biological and psychosocial factors with particular influence from epilepsy. Further research is required to achieve an evidence base for treatment. WHAT THIS PAPER ADDS: Over half of children with hypothalamic hamartoma present with psychiatric comorbidity. Externalizing and internalizing disorders are present in approximately 60% and 30% of children with hypothalamic hamartomas respectively. Epilepsy and male sex are associated with externalizing psychopathology. Intellectual disability mediates the association between epilepsy and externalizing symptoms. No clear associations are evident for internalizing disorders or precocious puberty.

PERFIL NEUROPSIQUIÁTRICO DEL HAMARTOMA HIPOTALÁMICO EN PEDIATRÍA: REVISIÓN SISTEMÁTICA Y SERIE DE CASOS: OBJETIVO: Evaluar las comorbilidades neuropsiquiátricas en niños y adolescentes con hamartoma hipotalámico. MÉTODO: En este estudio analizamos retrospectivamente las notas de los casos de todos los individuos con hamartoma hipotalámicos referidos al Great Ormond Street Hospital, London, entre el 2000 y 2016. Además, realizamos una revisión bibliográfica sistemática dirigida a identificar la serie de casos pediátricos. Síntomas psiquiátricos, demográfico, comorbilidades físicas y funcionamiento cognitivo fueron recolectados en todos los casos posibles.Se efectuaron análisis para determinar qué factores se asociaron con psicopatología y se investigaron mecanismos potenciales. RESULTADOS: En total 46 casos fueron incluidos en la serie de casos (28 masculinos, 18 femeninos, media de edad a la evaluación 11 años y 8 meses, DS 4 años y 0 mes). La revisión bibliográfica identifico 29 artículos describiendo 264 casos que reunieron criterios de inclusión para la extracción de datos. En total, al menos 50% de casos presentaban psicopatología. Epilepsia, discapacidad intelectual, y sexo masculino fueron asociados con desórdenes externos (déficit de atención con hiperactividad, desórdenes conductuales y oposicional desafiante, ataques de furia). Ningún factor fue asociado con la internalización de desórdenes neuropsiquiátricos (desórdenes de ansiedad y depresión), aunque éstos no fueron bien reportados. INTERPRETACIÓN: Las comorbilidades psiquiátricas son altamente prevalentes en la presentación del hamartoma hipotalámico pediátrico. La etiología de la psicopatología comprende un rango de interacciones biológicas y factores psicosociales con particular influencia de la epilepsia. Se requiere más información de investigación para reunir evidencia científica que guie el tratamiento.

PERFIL NEUROPSIQUIÁTRICO DO HAMARTOMA HIPOTALÂMICO PEDIÁTRICO: REVISÃO SISTEMÁTICA E SÉRIE DE CASOS: OBJETIVO: Avaliar comorbidades neuropsiquiátricas em crianças e adolescentes com hamartoma hipotalâmico. MÉTODO: Nós analisamos retrospectivamente os registros de casos de todos os indivíduos encaminhados para o Hospital Great Ormond Street, Londres, entre 2000 e 2016. Além disso, uma revisão sistemática visando identificar todos os casos pediátricos prévios foi realizada. Sintomas psiquiátricos, dados demográficos, comorbidades físicas, e funcionamento cognitivo foram registrados para todos os casos em que foi possível. Análises foram realizadas para determinar quais fatores se associavam com psicopatologia e potenciais mecanismos foram investigados. RESULTADOS: Quarenta e seis casos foram incluídos na série de casos (28 do sexo masculino, 18 do sexo feminino; média de idade na avaliação 11a 8m (1a 11m-16a 11m, DP 4a 0m). Vinte e nove artigos representando dados de 264 casos atenderam aos critérios de inclusão para a revisão sistemática. No total, pelo menos 50% dos casos apresentaram psicopatologia. Epilepsia, deficiência intelectual, e sexo masculino eram associados com desordens externalizantes (transtorno de déficit de atenção e hiperatividade, transtornos de conduta e de desafio oposicional, e ataques de raiva). A deficiência intelectual mediou os efeitos da epilepsia e da psicopatologia externalizante. Nenhum fator foi associado com transtornos internalizantes (ansiedade e transtornos depressivos), embora estes não tenham sido bem reportados. INTERPRETAÇÃO: Comorbidades psiquiátricas são altamente prevalentes na apresentação do hamartoma hipotalâmico pediátrico. A etiologia da psicopatologia envolve uma variedade de fatores biológicos e psicossociais que interagem, com particular influência da epilepsia. Mais pesquisas são necessárias para se atingir uma base de evidências para o tratamento.

Syringocystadenoma papilliferum arising in a naevus sebaceous.

Naevus sebaceus is a cutaneous hamartoma with the potential of developing into benign or malignant neoplasms. Syringocystadenoma papilliferum (SCAP) have been reported to originate from naevus sebaceus. SCAP is a rare, benign adnexal skin tumour of apocrine or eccrine type of differentiation which typically presents as a nodule or a plaque on the scalp or face. We report a case of syringocystadenoma papilliferum arising in an undiagnosed pre-existing naevus sebaceus in a 56-year-old female.

Psychiatric comorbidity with hypothalamic hamartoma: Systematic review for predictive clinical features.

OBJECTIVE: We conducted a systematic review of the English-language literature to identify clinical features associated with a higher risk of psychiatric symptoms (aggression and rage behaviors) in patients with hypothalamic hamartoma (HH) and epilepsy. METHODS: Two publicly-accessible databases (PubMed and Cochrane Library) were searched for Hypothalamic Hamartoma AND Epilepsy. We identified peer-reviewed original research publications (case reports or clinical series; N=19) in which clinical data was provided on an individual basis. Subjects were cohorted into those with (N=51) and without (N=68) behavioral aggression. Multiple clinical features were collated and subjected to univariate analysis to determine possible differences between these two cohorts. RESULTS: The presence of aggression significantly correlated with 1) male gender, 2) younger age at time of first seizure onset, 3) the presence of intellectual disability, and 4) the presence of multiple seizure types (versus gelastic seizures only). For those patients undergoing surgical treatment, aggression also correlated with younger age at the time of surgical intervention. CONCLUSION: Possible predictive clinical features for the presence of aggression and rage behaviors in patients with hypothalamic hamartoma and epilepsy are identified. These results may contribute to the complex treatment decisions that are unique to this population.

Chronic Obstructive Pulmonary Disease Mismatch: A Case of Tracheal Hamartoma.

OBJECTIVE: To demonstrate the diagnostic challenge of tracheal hamartoma in a patient with chronic obstructive pulmonary disease (COPD). CLINICAL PRESENTATION AND INTERVENTION: A 65-year-old man with COPD was admitted with sudden onset of asphyxia attacks related to the position of his body. Computerized tomography (CT) of the neck showed a soft tissue mass with calcification, which occluded more than two-thirds of the proximal part of the trachea. The tumor was completely removed, and histopathology confirmed hamartoma. CONCLUSION: This case report showed the detection of a primary tracheal tumor on CT. This finding enabled the correct diagnosis and led to appropriate treatment in the form of surgery.

Hair and Scalp Disorders in a Tuscan Pediatric Dermatological Outpatient Clinic: A Clinical and Epidemiological Evaluation.

OBJECTIVES: The aim of this study was to evaluate the clinical and epidemiological profile of hair and scalp disorders in children referred to the Pediatric Dermatology Outpatient Clinic. MATERIALS AND METHODS: We performed a retrospective study of children with hair loss problems or scalp diseases who turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital, Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics, personal and familial medical history, laboratory tests, clinical examination, final diagnosis and therapeutic interventions were obtained from the manual chart review. RESULTS: Of the 2,640 children who had access to the Pediatric Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190 children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had infections and 2 (1.05%) had infestation of the scalp. A case of constitutional hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were diagnosed. CONCLUSIONS: Our results underline that hair and scalp diseases represent an important percentage of admittances to a dermatological pediatric outpatient clinic. The variety and complexity of the diseases observed in this study included diseases commonly found also in adulthood.

[Evolution of ideas and techniques, and future prospects in epilepsy surgery]. / Évolution des idées et des techniques, et perspectives d'avenir en chirurgie de l'épilepsie.

INTRODUCTION: The aim of this article was to review and evaluate the published literature related to the outcome of epilepsy surgery, while placing it in an historical perspective, and to describe the future prospects in this field. STATE OF ART: Temporal lobe surgery achieves seizure freedom in about 70% of cases. Seizure outcome is similar in the pediatric population. Extratemporal resections impart good results to 40% to 60% of patients, with a better prognosis in the case of frontal lobe surgery. Pediatric hemispherotomy leads to seizure control in about 80% of children. Radiosurgery used as a treatment for temporal mesial epilepsy has an outcome quite similar to that obtained with surgical resection, but provides a neuropsychological advantage. Radiosurgery is also effective in 60% of children treated for seizures related to hypothalamic hamartoma. Regarding palliative surgery, callosotomy and multiple subpial transections show satisfactory outcomes in over 60% of cases. Neuromodulation techniques (vagus nerve stimulation and bilateral stimulation of the anterior nucleus of the thalamus) allow a 50% reduction of seizures in half of patients. PERSPECTIVES: Transcranial magnetic stimulation combined with electroencephalography seems a promising technique because of its diagnostic, prognostic and therapeutic applications. Transcranial ultrasound stimulation, which can reversibly control neuronal activity, is also under consideration. Concerning neuromodulation, trigeminal nerve stimulation may become an alternative to vagus nerve stimulation; while other targets of deep brain stimulation are being evaluated. Also, the possibility of coupling SEEG seizure focus detection with concomitant laser or radiofrequency focus destruction is under development. CONCLUSIONS: Constant evolution of epilepsy surgery has improved patient outcomes over time. Current research and development axes suggest the continuation of this trend and a reduction of the invasiveness of surgical procedures.

[Head and neck hamartomas: 10 years of experience at the Charité--University Medical Center Berlin]. / Hamartome im Kopf-Hals-Bereich: 10 Jahre Erfahrung an der Charité--Universitätsmedizin Berlin.

BACKGROUND: Head and neck tumors are rare entities in neonates. Hamartomas are benign congenital neoplasms. To date, there is a lack of sufficient epidemiological data concerning hamartomas in the field of otorhinolaryngology. MATERIALS AND METHODS: We retrospectively analyzed experiences at the Charité over the past 10 years in an ICD-10-based manner. Our otorhinolaryngology department maintains close cooperation with the level 1 perinatal center on our campus. RESULTS: The authors identified 3 patients suffering from fibrous hamartomas. This corresponds to an incidence of 2-3/30,000 newborns. The clinical aspects and courses are described in detail. Experiences with the management of hamartomas obstructing the upper aerodigestive tract are described. CONCLUSION: Head and neck hamartomas are very rare malformations. They possess the ability to cause otorhinolaryngological emergencies in newborns. Interdisciplinary management and histological assessment are mandatory. Anmerkung.

[Hypothalamic hamartoma in paediatric patients: clinical characteristics, outcomes and review of the literature]. / Hamartoma hipotalámico en la edad pediátrica: características clínicas, evolución y revisión de la literatura.

OBJECTIVE: To describe the epidemiological and clinical-electroencephalographic characteristics, and associated morbidity of patients with hypothalamic hamartoma, as well as the treatment followed and outcomes PATIENTS AND METHODS: We have retrospectively reviewed the medical histories of 10 patients diagnosed with hypothalamic hamartoma by magnetic resonance imaging over the last 20 years. RESULTS: The age of onset of epilepsy in patients with hypothalamic hamartoma in our series was between the first days of life and 2 years. Of the 10 total patients, 8 had epileptic seizures during its progress. All of them had gelastic seizures, in addition to other types of seizures, with the most common being partial simple seizures. The electroencephalographic findings recorded were highly variable. One of the patients developed epileptic encephalopathy. Five patients had some kind of conduct disorder. Five patients had cognitive problems. At least 2 different antiepileptic drugs were measured in 8 of the patients who had seizures, and in 6 of these some type of non-pharmacological treatment had been used with the objective of seizure control. Only in 3 of 8 patients has been achieved Acceptable control of epilepsy had only been achieved in 3 out the 8 patients. Five patients of the series developed precocious puberty. The average time of follow-up of the series was approximately 6 years. CONCLUSIONS: Epilepsy is the most frequent manifestation of hypothalamic hamartomas. Most cases were drug-resistant, which led to difficulties in the management of these patients, requiring surgery for their control on many occasions. Psychiatric comorbidity and cognitive impairment is common.

Prevalence of respiratory epithelial adenomatoid hamartomas (REAH) associated with nasal polyposis: an epidemiological study - how to diagnose.

OBJECTIVES: To highlight the prevalence of respiratory epithelial adenomatoid hamartomas in the olfactory cleft of patients with nasal polyposis. To demonstrate characteristics indicative of hamartoma on the CT scans of paranasal sinuses during surgery and in histopathological exams. METHODS: Cross-sectional study carried out in Hospital das Clínicas da UFMG and Núcleo de Otorrino BH. We performed 114 nasal endoscopic surgeries for polyposis, between February 2015 and November 2019. We assessed the olfactory cleft width in all preoperative CT scans. Upon seeing an indication of hamartoma on the CT scan, we took a tissue sample from the olfactory cleft during the surgery and sent for histopathological exam. We referred the samples to a pathologist experienced in the anatomopathological diagnosis of respiratory epithelial adenomatoid hamartomas. RESULTS: Of the 114 patients with polyposis, 54 (47.4%) had olfactory cleft enlargement and, 100% of them had tissue with a dense and hardened polypoid aspect, with a slight cerebriform appearance in this region during the surgery. Histology confirmed a respiratory epithelial adenomatoid hamartoma. CONCLUSION: This observation suggests that the presence of hamartomas in polyposis is common, but underdiagnosed. LEVEL OF EVIDENCE: Step 3 (Level 3).

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.

Management of nevus sebaceous and the risk of Basal cell carcinoma: an 18-year review.

Nevus sebaceous (NS) is a common congenital hamartoma of the skin, usually found on the head and neck. It may undergo malignant transformation to basal cell carcinoma (BCC). However the incidence and lifetime risk of malignant transformation is unknown. We performed an 18-year review of all NS excisions at our institution, to report the number of cases of BCC and other neoplasms within excised NS. The aim is to inform physicians who must weigh the risks in recommending excision of a NS in a pediatric patient population with the risk of malignancy. After a database query for years 1990-2008, charts were reviewed and data were extracted on demographics and surgical history relating to NS. Thirty-one NS with abnormal findings were reviewed microscopically by a dermatopathologist. There were 651 NS distinct lesions among 631 patients and 690 excisions. Twenty-one intralesional diagnoses were found in 18 patients. Five patients (0.8%) had BCC (mean age 12.5 yrs, range 9.7-17.4 yrs). Seven (1.1%) had syringocystadenoma papilliferum (SP) (mean age 8.8 yrs, range 1.7-16.9 yrs), a lesion that may undergo malignant transformation. Malignant transformation of NS can occur in childhood or adolescence. We believe all NS should be excised, however timing of excision can be flexible. Our data do not support age cutoffs or morphologic changes to determine optimal excision time. In conjunction with the treating physician, the parent and patient may weigh the small risk of malignant transformation of NS against the morbidity associated with excision and anesthesia.

Tumours of peripheral nerves in the upper extremity: a 22-year epidemiological study.

Peripheral nerve tumours are uncommon. Our aims were to calculate the incidence and relative frequencies, to define sites of nerve tumours and to judge preoperative symptoms and outcomes of intervention. The results of 53 patients, with 68 tumours and histopathological diagnoses of true neoplasms, who had been operated on at the Department of Hand Surgery, Malmo, Sweden, between 1986 and 2007, were analysed. Schwannomas were the most common tumour (n=42). The incidence of schwannomas was 0.62/100 000 inhabitants/year in Malmo during that time period. The median nerve was most affected, closely followed by the ulnar and digital nerves. The preferred sites were the forearm, the thumb, and the digits. The most common preoperative symptom was pain. Loss of sensation was the most common postoperative complication. However, 33/53 patients (62%) were completely free of symptoms after excision. Patients should be provided with meticulous information preoperatively.

Hypothalamic hamartomas in adulthood: Clinical spectrum and treatment outcome-A unicenter experience.

INTRODUCTION: Clinical manifestations of the hypothalamic hamartoma-epilepsy syndrome (HH-ES) in adulthood are variable. Efficacy of therapeutic options and outcome are diverse. METHODS: Retrospective study of adult patients diagnosed with a HH in magnetic resonance imaging and epilepsy who attended our tertiary Epilepsy Unit between 2003 and 2018. We report the clinical and electroencephalographic features of a series of adult patients with HH and related epilepsy seen in our center together with the treatments and seizure outcome. RESULTS: We describe a series of eight patients. Five males (62.5%), median age at evaluation was 28.5 years (IQR: 15.5). Clinical manifestations included focal with preserved and impaired awareness emotional seizures (gelastic seizures [GS]) in six patients (75%), focal tonic, atonic with impaired awareness and focal to bilateral tonic-clonic seizures. Mild GS were the only symptom in one patient. Three patients (37.5%) had endocrinological disturbances such as obesity and hypothyroidism. Fifty percent of the patients showed psychiatric comorbidity such as anxiety disorder and aggressiveness, and two patients had psychomotor delay. Seven patients (87.7%) had drug-resistant seizures and three of them were treated with radiosurgery. Out of the treated group, only one (33.3%) became seizure-free 2 years after surgery but developed psychiatric problems. The other two patients had an Engel IV outcome and received a vagal nerve stimulation (VNS) implant. VNS did not lead to changes either in intensity nor in seizure frequency. CONCLUSIONS: Hypothalamic hamartoma-epilepsy syndrome clinical manifestations in adult patients are as variable as at pediatric age. Outcome of therapeutic options such as radiosurgery or VNS may be poorer at this stage.

Incidence and cytological features of pulmonary hamartomas indeterminate on CT scan.

OBJECTIVE: Pulmonary hamartomas have a characteristic heterogeneous radiological appearance. However, when composed predominantly of undifferentiated mesenchymal fibromyxoid component, their homogeneous appearance on computed tomography is indeterminate for malignancy. Rendering an accurate preoperative diagnosis in these cases can alter management. The aim of this study was to determine the incidence and accuracy of cytodiagnosis for hamartomas 'indeterminate' by imaging. METHODS: We retrospectively reviewed records for hamartomas diagnosed by transthoracic fine needle aspiration (FNA) including immediate impressions and final diagnoses. Cytological features evaluated included the presence of fibromyxoid stroma, bronchioloalveolar cell hyperplasia, fibroadipose tissue, cartilage and smooth muscle. RESULTS: Eighteen (1.3%) hamartomas were identified from 1355 transthoracic FNAs. The immediate impression was hamartoma in 13 (72%), carcinoid in one (6%), mucinous bronchioloalveolar carcinoma in two (11%) and non-diagnostic in two (11%). The final diagnosis of hamartoma in cases diagnosed as carcinoid, mucinous bronchioloalaveolar carcinoma and non-diagnostic on immediate impression was rendered following assessment of all cytological material. CONCLUSION: Overall, FNAs are highly reliable for diagnosing hamartomas even when composed principally of undifferentiated mesenchymal fibromyxoid stroma, especially with the aid of all available preparations including Diff-Quik smears, Papanicolaou smears, ThinPreps and cell block material.

[Most common benign epithelial breast diseases: diagnosis, treatment and cancer risk]. / Les principales lésions mammaires épithéliales bénignes et à risque. Prise en charge diagnostique et thérapeutique.

As a consequence of breast imaging development and increased interventional radiology, benign epithelial breast diseases (BEBD) represent a growing percentage of breast pathology diagnoses. BEBD include numerous entities such as cysts, fibrosis, adenosis, duct ectasia, which require neither surgery nor follow-up. Some BEBD have to be individualized (radial scars, papillomas, complex sclerosing adenosis, lobular intraepithelial neoplasia, flat epithelial atypia, atypical hyperplasia), being preinvasive lesions or markers of increased breast cancer risk, or being associated with suspect radiological aspect. BEBD should be managed in a pluridisciplinar way and correctly diagnosed by percutaneous biopsies or surgical specimens. The goals of surgery vary according to lesions. It always allows a complete surgical specimen analysis and therefore a search for atypical or cancerous cells. Surgery can also have a preventive role by reducing the risk of potential malignant transformation. Finally, it enables in some cases the excision of a radiologically suspect mass. So the aim of this review is to give a clinical and morphological description of most common BEBD, underlying their cancer risk, specific diagnosis, therapeutic, follow-up and psychological repercussions.

Syndromic sebaceous nevus: current findings.

BACKGROUND: Sebaceous nevus is a congenital malformation of the skin that usually occurs on the scalp or face. Syndromic forms do rarely exist with associated cerebral and ocular malformations. The skin lesions are pale at birth and become irregular by puberty. In the adult patient, tumors (usually benign) develop from sebaceous nevus. Their surgical excision during childhood can give a better result in terms of the definitive scar. OBJECTIVES: The aim of this study is to analyze our cases of syndromic sebaceous hamartoma, perform a review of the existing literature, and propose guidelines for the therapeutic plan. METHODS: This is a retrospective study reviewing the cases of syndromic sebaceous nevus treated in the Department of Orthopedic Plastic Pediatric Surgery in Montpellier, France, and the Department of Pediatric Surgery in Lausanne, Switzerland, between 1994 and 2016. RESULTS: The files of six patients with syndromic sebaceous nevus were analyzed. The average age at the first consultation was 4 months. The location was craniofacial in all cases. Cerebral radiological imaging was performed on all patients; two showed abnormal findings. Four patients underwent ophthalmic examination, which all revealed abnormalities. Three patients had other associated malformations. Three patients presented with epilepsy or learning difficulties in the course of follow-up. CONCLUSION: All patients presenting with extensive sebaceous nevus of the craniofacial region should benefit from cerebral imagery and ophthalmic examination since there is a very high probability of associated abnormalities. The developmental problems encountered could not be definitively associated with the skin malformations.

Pediatric-onset gelastic seizures: clinical data and outcome.

Gelastic seizures are an extremely rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. The objective was to survey all Israeli children found to develop recurrent gelastic seizures and report presenting symptoms, electroencephalographic and radiologic data, and response to either antiepileptic drugs or surgery. Ten children who developed gelastic seizures at the age of 1 week to 6.5 years (mean, 25 months) at a frequency from 3 bouts per week to >10 prolonged bouts per day were followed for a period of 1.3-12 years (mean, 6 years). Seven cases were defined as symptomatic: cortical magnetic resonance imaging revealed a hypothalamic hamartoma in four patients and cortical abnormalities in three others. Seizure control was achieved in four patients, including a neonate with status gelasticus and hypothalamic hamartoma, and partial control in one more. Five children remained resistant to polytherapy, including three with hypothalamic hamartoma even after two of them underwent hemartoma excision. Thus, children with gelastic seizures may respond relatively well to drug therapy. Four of the 10 patients became seizure free with drug therapy; in three intractable symptomatic cases, surgery was tried but failed in two of the three.

Giant Brunner's hamartomas of the duodenum and obstructive jaundice. An overview of the literature and suspicion of malignancy in a case.

BACKGROUND/AIMS: 150 cases of Brunner's gland hamartoma (BGH) have been reported in the literature. BGHs are benign and are thought not to cause bile obstruction. METHODS: In this case report, a 60-year-old male is presented with unexplained obstructive jaundice who was also known for over 17 years with diffuse adenomatous hyperplasia of Brunner's glands in the duodenum. Despite the benign preoperative diagnosis, the choice of treatment was Whipple's procedure due to suspicion of a coexisting malignancy. RESULTS: Pathological analysis of the resection specimen revealed multiple BGHs and an adenocarcinoma of the papilla of Vater (PoV). Molecular pathology using loss of heterogeneity analysis was used to confirm that both were different entities. CONCLUSION: It is likely that previous reports of malignant degeneration of BGHs may actually have been cases involving the coexistence of a PoV adenocarcinoma. Physicians need to be alert when a patient presents with BGH accompanied with obstructive jaundice for simultaneously occurring PoV adenocarcinoma.

Epidermal nevus syndromes.

The term "epidermal nevus syndrome" (ENS) has been used to describe the association of epidermal hamartomas and extra-cutaneous abnormalities. Epidermal nevi follow the lines of Blaschko. The majority of the extra-cutaneous manifestations involve the brain, eye, and skeletal systems. Several subsets with characteristic features have been delineated including the nevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, Becker nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Epidermal nevi have been associated with benign and malignant neoplasms. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach. Amelioration of the cutaneous features of ENS has been difficult but there have been advances, especially in the use of lasers.