Biomedical subjects
Publications and source records attributed to Y Mikaeloff.
Lambert-Eaton myasthenic syndrome is a paraneoplasic syndrome which can reveal a primitive tumor. Frequently, the first diagnosis is myasthenia gravis. This disease is extremely rare in children. Only 10 cases have been reported in the last 35 years. We report 2 new observations occurring in very young patients, aged 2 and 3 years, with a ganglioneurobastoma as primitive tumor.
PURPOSE: To describe the characteristics of a previously overlooked devastating epileptic encephalopathy that presents as intractable bilateral perisylvian epilepsy starting with prolonged status epilepticus (SE) in normally developing school-aged children. METHODS: Retrospective study over 7 years of all normally developing children admitted in our institution for a prolonged SE following non-specific febrile illness with at least one seizure recorded on EEG. RESULTS: Fourteen children were included at a median age of 7.5 years (4-11) (median follow-up of 4 years (1-7)). Intractable SE lasted 4-60 days (median 30). CSF cell count was normal in five cases and moderately increased in the others. During SE, seizures were recorded in 11 patients and involved temporal lobes in 7; the other 4 patients exhibited perisylvian clinical features with secondary generalization. Intractable epilepsy followed SE in all cases without any latent period. Persisting seizures were recorded in 10 patients and involved temporo-perisylvian regions in 8, frontal regions in 2; 3 others had perisylvian ictal semiology. Spiking was bilateral in 10 cases. MRI showed bilateral hippocampal hypersignal and/or atrophy in 10 cases (extended to the neocortex in 3). All children had major cognitive sequelae. When feasible (six patients), detailed neuropsychology suggested fronto-temporal impairment. CONCLUSIONS: Among so called grey matter encephalitis patients, we identified a recognizable pattern we propose to call Devastating Epileptic encephalopathy in School-age Children (DESC) that begins with prolonged SE triggered by fever of unknown cause, and persists as intractable perisylvian epilepsy with severe cognitive deterioration.
Multiple sclerosis can develop during childhood, even among children under 10 years of age, and the initial diagnosis can be difficult. A first demyelinating event in children may be an episode of monophasic acute disseminated encephalomyelitis or a first episode of a macrophage activation syndrome, angiitis affecting the central nervous system or MS. The risk of developing MS is lower if: the child is younger than 10 years old; onset is associated with severely altered consciousness; presentation is polysymptomatic; or there are large and poorly limited lesions of the white matter. MS in children probably has a slightly better outcome than MS in adults. Initial treatment mainly relies on methylprednisolone, and there is little information on the results of beta interferon treatment in children with MS.
OBJECTIVE: Multiple sclerosis (MS) is by far the most popular diagnosis for patients with multifocal neurological disease. Owing to demyelinating inflammatory non-necrotic plaques of the white matter, MS can give remitting symptoms of virtually every part of the central nervous system. Corticosteroids are usually helpful. Devic's neuromyelitis optica (DNMO) is a neurological disease involving only the optic nerves and the spinal cord, where demyelination evolves towards necrosis and atrophy; the prognosis is poor and no satisfactory treatment is known. The objectives of this study are to describe clinical, biological, pathological and radiological data of patients with DNMO and to differentiate DNMO from MS. MATERIAL AND METHODS: We studied the files of 14 patients diagnosed with possible DNMO in three French hospitals between 1980 and 1999 and reviewed the literature. RESULTS: Nine patients were included as definite DNMO. Five were excluded because they did not fulfil the diagnostic criteria. For the nine patients with definite DNMO, DNMO was either monophasic or multiphasic. The prognosis was generally poor: two patients died and five others developed severe disability such as blindness, para or quadriplegia or both. Cerebrospinal fluid study and neuroimaging were essential to confirm the diagnosis of DNMO. Various immunosuppressive treatments generally failed to benefit the patients. CONCLUSION: In the literature (as well as our 14 initial patients) only a few cases of patients described as suffering from DNMO fulfilled the diagnostic criteria. The others showed evidence that another disease like MS was involved. We stress that inclusion and exclusion criteria have to be kept in mind to differentiate clearly DNMO from MS and other central nervous system white matter diseases.
OBJECTIVE: Congenital disorders of glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndromes, constitute a newly identified group of multisystem disorders characterized by defective glycosylation of N-glycosylated proteins. The objective of this work was to describe precisely neurological findings in patients with type Ia CDG (CDG-Ia) and to compare our results with the literature. STUDY DESIGN: We retrospectively reviewed neurological and neurodevelopmental, neuroimaging, and genetic features in ten patients with CDG-Ia who mainly presented with neurological abnormalities during childhood and therefore were referred to a neuropediatrician or a neurogeneticist. RESULTS: Neurological manifestations had a static clinical course, dominated by mental retardation and cerebellar dysfunction, and acute episodes: stroke-like episodes and seizures. However, microcephaly, retinopathy, and polyneuropathy were progressive. All patients had severe global neurodevelopmental delay: only one was able to walk alone at ten years of age and only one could read. Marked heterogeneity in manifestations and delay of diagnosis was noted across the patients. Cerebellar hypoplasia was found by magnetic resonance imaging in all ten patients and olivopontocerebellar hypoplasia in four patients. As in the literature, there was no clear phenotype-mutation correlation. CONCLUSION: Our findings confirm the importance of a precise and complete description of the neurological and neuroradiological phenotype delineating the phenotype of CDG-Ia to increase the likelihood of diagnosing the disease.
UNLABELLED: The aim of this study was to analyse the outcome of optic pathway gliomas in 30 children with neurofibromatosis type 1, the indications of treatment, and the follow-up and screening protocol. PATIENTS AND METHODS: All patients with a minimal two years follow-up (median six years, range two to 19 years), in two multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan (Toulouse) hospitals, were included in the study. In our series, we practiced systematic screening MRI in children under six years' of age or with neuropsychological deficiency that may imply an unreliable ophthalmological examination. RESULTS: Thirty-seven percent (11 patients) had progressive ophthalmological signs and were treated, and 63% (19 patients) were not progressive. Our study confirmed that most of optic pathway gliomas were stable during evolution, but rare cases may have bad prognosis. CONCLUSION: Our study supported the importance of close ophthalmological follow-up during childhood for which screening methods are discussed. There is a consensus to limit treatment for patients with progressive ophthalmological symptoms.
AIM: We studied the use of premixed nitrous oxide and oxygen in 80 patients with neurologic diseases. PATIENTS AND METHODS: Mean ages ranged 10 +/- 5 yrs. Twenty-three patients (29%) were mentally retardated among which 17 of them presented with severe epilepsy. Painful procedures consisted of: lumbar punctures (80%), intravenous access (7), gastric endoscopy (6), skin biopsy (4), gastrostomy tube management (3). High-risk children were continuously monitored using ECG, non invasive blood pressure and transcutaneous oxygen saturation. We studied acceptation of the inhalation, vital signs, satisfaction of children, parents, medical and nursing staffs; side effects were compared with a group of healthy children undergoing venous access before induction of anesthesia. RESULTS AND DISCUSSION: Acceptation increased with age. No significant changes in vital signs variables were observed. Satisfaction rate regarding the method was 88% for all children, parents, physicians and nurses. No serious undesirable event (as respiratory depression, seizure, inhalation of gastric content) occurred in these patients. The more frequent side-effects were: drowsiness during and after inhalation (35 and 9% respectively in the handicapped patients); nausea and vomiting (8%), headaches (3%), were more frequent than reported in literature but there were 25% of meningitis among our patients. CONCLUSION: Premixed nitrous oxide and oxygen was effective for reducing procedural pain and anxiety in children with neurological disorders, even in severely handicapped patients, with minor side-effects.
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We present a report of the use of interferon-beta before 18 years of age in 16 patients with childhood-onset multiple sclerosis. This study demonstrated that the treatment is safe and well tolerated.
BACKGROUND: Alternating hemiplegia of childhood is a syndrome which begins in the first year of life. It is characterized by repeated attacks of uni-or bilateral hemiplegia or hemiparesia. In most cases paroxysmal manifestations are observed: movements or dystonia++ attacks, episodic nystagmus, abnormal eye movements and disturbance of the neurovegetative system, predominantly in the first year of life. ANALYSIS: In half of the cases, neurological anomalies begin during the neonatal period with a non characteristic aspect. Typical attacks take place after one year of life, sometimes associated with partial epilepsy. In a quarter of cases, the oculomotor anomalies have been known since early life. The diagnosis is made prior to one year on the basis of associated oculomotor anomalies and other symptoms without EEG arguments for epilepsy. Paroxysmal nystagmus is always found. One eye is affect in most cases, generally with horizontal and seldom with vertical movements of large variable pendular amplitude. One eye with nystagmus and the other with mydriasis is sometimes reported. Most attacks last from 30 sec to 3 min. Paroxysmal strabismus described in half of the cases seems to be generally unilateral internuclear transitory ophthalmoplegia. Finally, ocular deviations on the hemiparetic side are described. They are generally unique or sometimes associated with head deviation. Spontaneous blinking is reduced. CONCLUSION: Alternating hemiplegia of childhood is a non-epileptic sporadic, paroxysmal manifestation of unknown pathogenesis. Prognosis is poor. The presence of oculomotor signs suggests the diagnosis.
West syndrome is an epileptic encephalopathy which includes psychomotor deterioration. In rare cases, it is due to an inherited, progressive metabolic disease. We report a 2 year-old child with dihydropteridine reductase deficiency who developed hypsarrhythmia and infantile spasms which were documented on video-polygraphic EEG. Despite dietary restriction of phenylalanine, and oral administration of amine precursors, the initial course was unfavorable. A beneficial effect from hydrocortisone was then observed, with control of spasms and improvement of psychomotor delay.
What is the balance of benefits and risks of dexamethasone in extremely immature infants? The answer remains unclear. We feel that the risks of "early" treatment outweigh the benefits, because many infants who would not develop CLD will be treated. Treatment between day 7 and day 14 seems more appropriate to us, as it focuses on infants with a high risk of developing CLD. However, the lungs may be already somewhat damaged when starting treatment, whose expected benefit is a shortened duration of mechanical ventilation and a decreased incidence of CLD. The risks for growth and brain development are not clearly assessed. Both 7-day courses and pulse therapy are effective, but no comparison of these 2 schedules has been published. We therefore do not know whether pulse therapy provides the same benefits as 7-day courses with fewer risks for growth or cardiomyopathy.
BACKGROUND: Symptomatic forms of hyperphenylalaninemia are rare in France since neonatal screening began. CASE REPORT: A child born in Algeria from consanguinous parents was referred at 2 years of age for a severe epileptic encephalopathy with hypotonia. Amino acid chromatography revealed hyperphenylalaninemia due to a dihydropteridine reductase deficiency. Dietary restriction of phenylalanine and oral administration of amine precursors, L-dopa and 5-hydroxytryptophan had poor efficiency on epilepsy and psychomotor delay. CONCLUSION: Diagnosis of hyperphenylalaninemia must be evoked in any children with progressive encephalopathy born in country where neonatal screening is not performed.
We present a retrospective study of 30 cases of primitive cerebral neuroectodermal tumors (PNET), excluding medulloblastomas, referred to us postoperatively for additional therapy to evaluate prognostic factors and treatment efficiency. The histologic types were: pinealoblastomas (n = 7); ependymoblastomas (n = 2); medulloepitheliomas (n = 4), and other PNET (n = 17). The tumor was located in the supratentorial area in 24 patients and in the posterior fossa in 6 patients. Among the supratentorial tumors, 8 were metastatic. Maximal surgical resection was performed. Sixteen of 30 patients had no measurable disease after surgery and were considered as standard-risk (SR) cases, and 14 with a local residue or metastasis as high-risk (HR) cases. The objective of postsurgical treatment was to avoid radiotherapy in children below 4 years of age. It consisted of radiotherapy alone in 6 patients, chemotherapy alone in 17, and radiotherapy with chemotherapy in 7. Furthermore, high-dose chemotherapy (busulfan, thiotepa) and autologous bone marrow transplantation, performed in 6 patients, yielded a response rate of 3/6. Event-free survival (EFS) of SR patients was 37% at 3 years (95% confidence interval (CI) 14-60%) and overall survival 44% (95% CI 26-62%). Only 1 of the HR patients achieved a complete remission and all of them died early. The critical prognostic factors appear to be the completeness of initial surgical resection and absence of metastasis. These tumors have a poor prognosis. Novel strategies (high-dose chemotherapy) are needed to improve their outcome because the children concerned are very young and the effects of radiotherapy are particularly deleterious when tumors are situated in the supratentorial area.
The myeloproliferative leukemia retrovirus (MPLV) has the v-mpl cellular sequences transduced in frame with the deleted and rearranged Friend murine leukemia virus env gene. The resulting env-mpl fusion oncogene is responsible for an acute myeloproliferative disorder induced in mice by MPLV. v-mpl is a truncated form of the c-mpl gene which encodes the receptor for thrombopoietin. We investigated the contribution of the Env-Mpl extracellular domain in the constitutive activation of this truncated cytokine receptor and found that the rearrangement of the env sequences in the env-mpl fusion gene was not required for oncogenicity. A pathogenic variant, DEL3MPLV, was generated, which differs from MPLV by the deletions of 22 amino acids of the Env signal peptide, all of the mature Env sequences, and 18 N-terminal amino acids of the v-Mpl extracellular domain. The resulting del3-mpl oncogene product conserves in its extracellular region the first 12 amino acids of the Env signal sequence including a cysteine residue, and 25 amino acids of the v-Mpl. We show here that a mutation converting this cysteine to a glycine completely abolishes del3-mpl oncogenicity and that the del3-mpl oncogene product is constitutively activated by disulfide-linked homodimerization.