ABSTRACT
OBJECTIVE: Functional hearing loss (FHL) is a disorder in which there are abnormal values on a hearing test, despite the absence of organic abnormalities in the peripheral and central auditory pathways. Here, we examined the developmental characteristics of FHL and the importance of intervention by analyzing the clinical characteristics of children with this disorder. METHODS: We retrospectively examined 16 patients assessed under a diagnosis of FHL. After interventions such as psychological counseling by our pediatrics and psychiatry departments, we compared the clinical profiles of patients in which hearing was "improved/normalized" and "unimproved". RESULTS: Fourteen patients visited a pediatrician and two chose not to do so. A discrepancy between the maximum and minimum values of the four index scores was observed in all patients in which WISC-IV (the fourth version of the Wechsler Intelligence Scale for Children) was performed (n = 12). The discrepancy between the verbal comprehension index (VCI) and perceptual reasoning index (PRI) was significantly greater in "unimproved" patients than in "improved/normalized" patients. Hearing improved, or was normalized, after intervention in six of 16 patients. CONCLUSIONS: Developmental imbalances were suspected in all 12 children who visited a pediatrician and completed the WISC-IV. Cooperation with pediatricians, psychiatrists, and other health professionals is desirable in supporting patients diagnosed with FHL.
Subject(s)
Hearing Loss, Functional , Humans , Child , Retrospective Studies , Hearing , Hearing Tests , Auditory PathwaysABSTRACT
BACKGROUND: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningitis and improved without treatment. CASE: A 13-year-old girl presented with fever, headache, decreased appetite, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and magnetic resonance imaging (MRI) showed leptomeningeal enhancement. The patient was diagnosed with aseptic meningitis at admission. However, there were no signs of recovery 4 days after admission (i.e., 8 days after disease onset). Therefore, we performed extensive investigations to identify the cause of the underlying infection and inflammation. On day 14 after admission, the serum MOG-Ab test performed at admission came back positive (1:128) and she was diagnosed with MOGAD. She was discharged on day 18 after admission, because her symptoms, CSF pleocytosis, and MRI findings had improved. About 6 weeks after discharge, MRI revealed hyperintensity without gadolinium enhancement. However, her serum MOG-Ab test was negative. We did follow-ups for 11 months but found no new neurological symptoms. DISCUSSION AND CONCLUSION: To the best of our knowledge, this is the first ever report of a pediatric patient with MOGAD experiencing spontaneous remission with no demyelinating symptoms during an extended follow-up period.
Subject(s)
Meningitis, Aseptic , Female , Humans , Autoantibodies , Contrast Media , Gadolinium , Leukocytosis , Myelin-Oligodendrocyte Glycoprotein , Remission, Spontaneous , AdolescentABSTRACT
BACKGROUND: The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature. CASE PRESENTATION: We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype. The patient had compound heterozygous variants of HEXB (p.Trp460Arg, p. Arg533His); the Trp460Arg was a novel variant. Long-term follow-up revealed no intellectual deterioration, swallowing dysfunction, or respiratory muscle dysfunction despite progressive weakness of the extremities and sensory disturbances. CONCLUSION: We need to be aware of Sandhoff disease in patients with juvenile-onset motor neuron disease.
Subject(s)
Motor Neuron Disease/etiology , Sandhoff Disease/genetics , Adult , Age of Onset , Follow-Up Studies , Humans , Phenotype , Sandhoff Disease/complicationsABSTRACT
OBJECTIVES: Long-term adrenocorticotropic therapy (LT-ACTH), which consisted of 2-4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT-ACTH for preventing WS relapse, as well as the prevalence of its adverse events. METHODS: This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT-ACTH. Clinical information of the patients and protocol of LT-ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan-Meier method. RESULTS: Clinical information of 16 children with WS was analyzed. The median age at LT-ACTH initiation was 14.5 months (range: 7-68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT-ACTH regimens comprised a median of 16 days of daily injections (range: 11-28 days) and 10 months of weekly injections (range: 3-22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%-80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. SIGNIFICANCE: Our study firstly explored the efficacy of LT-ACTH for preventing WS relapse. LT-ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.
Subject(s)
Spasms, Infantile , Adrenocorticotropic Hormone/adverse effects , Adrenocorticotropic Hormone/therapeutic use , Child , Humans , Recurrence , Research , Retrospective Studies , Spasms, Infantile/drug therapyABSTRACT
We report a patient with a 6q22.1 deletion, who presented with a rare syndrome of generalized epilepsy, myoclonic tremor, and intellectual disability. There was no clinical progression after follow-up for more than 10 years. Our report presents the genetic basis for a phenotype involving a non-progressive generalized epilepsy with tremor. The efficacy of valproic acid for seizure control and the partial efficacy of deep brain stimulation with propranolol for myoclonic tremor is detailed.
ABSTRACT
INTRODUCTION: There is increasing evidence that immunosuppressive therapy is essential for reducing disease activity and avoiding further attacks in patients positive for anti-myelin-oligodendrocyte glycoprotein (MOG) antibodies. However, to date, no placebo-controlled trial has been published. OBJECTIVE: We aimed to evaluate the long-term outcome and anti-MOG antibody titers of seropositive Japanese pediatric patients without long-term immunosuppressive therapy. METHODS: Of 11 consecutive patients positive for anti-MOG antibodies seen at Tohoku University Hospital from 1992 to 2013, 5 patients did not receive preventive long-term immunosuppressive treatment and had been followed up longitudinally (more than 60â¯months). RESULTS: The follow-up periods were 68-322â¯months (median, 150â¯months). The expanded disability status scale scores of all patients were 0 at the last observation. Three patients were negative for the antibody at the last follow-up, and the titers of the two patients whose anti-MOG antibodies were positive at the last follow-up were lower than at the first examinations. The interval to the second attack in three patients was 1-124â¯months (median, 33â¯months). Acute attacks were treated with methylprednisolone pulse therapy (four patients) or intravenous immunoglobulin (one patient). All patients achieved full recovery after acute therapy. Oral corticosteroid was tapered over a period of 6-26â¯weeks (median, 17â¯weeks). CONCLUSIONS: We reported our experience with very long-term follow-up of 5 Japanese pediatric patients with anti-MOG antibody-positive disease who did not receive long-term immunosuppressive therapy. Persistent positivity to anti-MOG antibody in some patients suggests the necessity for long-term follow up despite infrequent relapse.
Subject(s)
Encephalomyelitis/immunology , Immunotherapy , Myelin-Oligodendrocyte Glycoprotein/immunology , Autoantibodies/blood , Child , Child, Preschool , Encephalomyelitis/therapy , Female , Follow-Up Studies , Humans , Immunotherapy/methods , Infant , Longitudinal Studies , Male , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype-phenotype correlation. METHODS: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. RESULTS: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype-phenotype correlation did not emerge. CONCLUSION: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.
Subject(s)
Collagen Type IV/genetics , Nervous System Diseases/genetics , Nervous System Diseases/pathology , Adolescent , Adult , Child , Child, Preschool , Epilepsy/genetics , Female , Genetic Association Studies , Humans , Male , Mutation , Young AdultABSTRACT
OBJECTIVE: To understand cerebral brain dysfunction in patients with Dravet syndrome (DS), we conducted a [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) study in patients with DS whose SCN1A gene variant was confirmed. METHODS: FDG-PET was performed on eight patients with DS. A SCN1A mutation analysis revealed missense variants in four patients and truncation variants in four patients. The patients' ages at the time of the PET study were 2, 2, 2, 3, 6, 13, 20, and 29 years old, respectively. The patients' developmental/intelligence quotient at the time of the PET study were 62, 52, 64, 35, 30, 15, and <25, respectively. The mean standardized uptake value (SUV) was calculated in four segments (frontal, temporal, parietal, and occipital) for the semi-quantitative analysis of 18F-FDG uptake. This value represents the average of the regions of interest in each lobe and was divided by the average SUV of the cerebellar hemisphere of each patient and compared between the patients with DS and the diseased controls. RESULTS: Glucose uptake in patients with DS decreased significantly, particularly in those ≥6 years old. Importantly, a comparison between the younger and older patients with DS revealed that glucose uptake was normal in patients who were ≤3 years (2, 2, 2, and 3 years), whereas a profound reduction in glucose uptake in the fronto-temporo-parietal-occipital cortices was observed in patients ≥ 6 years (6, 13, 20, and 29 years). Magnetic resonance imaging revealed no detectable atrophic legions or other changes in the cerebral cortices of patients ≥ 6 years of age. SIGNIFICANCE: The present study showed a remarkable reduction in cerebral glucose metabolism in multiple lobes for the first time, which became obvious after the late infantile period. These findings may indicate a functional neuroimaging aspect of epileptic encephalopathy of DS or a feature of the SCN1A variant itself.
Subject(s)
Epilepsies, Myoclonic/diagnostic imaging , Epilepsies, Myoclonic/genetics , Fluorodeoxyglucose F18/pharmacokinetics , Mutation/genetics , NAV1.1 Voltage-Gated Sodium Channel/genetics , Positron-Emission Tomography , Adolescent , Adult , Cerebellum/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Child , Child, Preschool , Female , Functional Laterality , Glucose/metabolism , Humans , Male , Tomography Scanners, X-Ray Computed , Young AdultABSTRACT
Caveolinopathies, caused by CAV3 mutations, can include several phenotypes such as rippling muscle disease, limb-girdle muscular dystrophy type 1C, distal myopathy, familial hypertrophic cardiomyopathy, and idiopathic hyperCKemia. Here we present characteristic skeletal muscle imaging findings in four patients with genetically defined childhood-onset RMD caused by CAV3 mutations and in one patient with congenital generalized lipodystrophy type 4 with muscular dystrophy due to polymerase I and transcript release factor (PTRF) mutations, which may have caused secondary deficiency of caveolin-3. Muscle MRI revealed that the rectus femoris and semitendinosus muscles were most commonly affected in the rippling muscle disease patients. Peripheral changes in the rectus femoris were specific and observed even in one of the younger patients in this study. Furthermore, muscle involvement extended to the semitendinosus muscles, biceps femoris, and gracilis with disease progression or increase in its severity. Similar patterns of involvement were observed on reviewing skeletal muscle images of various previously reported phenotypes of caveolinopathy; interestingly, patients with secondary deficiency of caveolin due to PTRF mutations revealed the same pattern. Thus, primary caveolinopathies and secondary deficiency of caveolin demonstrated specific findings on skeletal muscle imaging, regardless of the broad phenotypic spectrum of these two conditions.
Subject(s)
Caveolins/genetics , Magnetic Resonance Imaging , Muscle, Skeletal/diagnostic imaging , Muscular Diseases/diagnostic imaging , Muscular Diseases/genetics , Adult , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , MaleABSTRACT
Long-term outcome of West syndrome with a NR2F1 mutation.
Subject(s)
COUP Transcription Factor I/genetics , Spasms, Infantile/genetics , Adult , Female , Humans , Infant , Mutation, Missense/genetics , Seizures/genetics , Seizures/pathology , Seizures/physiopathology , Spasms, Infantile/pathology , Spasms, Infantile/physiopathologyABSTRACT
We describe the first case of a successful functional hemispherectomy in a patient with epileptic encephalopathy and a de novo collagen type IV alpha 1 (COL4A1) mutation. A 4-year-old girl was COL4A1 mutation-positive and suffered from drug-resistant epilepsy, hemiplegia, and developmental delay. Magnetic resonance imaging detected no porencephaly, and she had no cataract or renal abnormality. Following a presurgical evaluation for epilepsy, she underwent a functional hemispherectomy. She has been seizure free with no intracranial hemorrhage or other perioperative complications. Patients with a COL4A1 mutation have an increased risk for intracranial hemorrhage because of disrupted integrity in the vascular basement membrane due to the mutation. After weighing the risks and benefits to these patients, epilepsy surgery may not be absolutely contraindicated. Furthermore, pediatric neurologists should be aware of an undiagnosed COL4A1 mutation when a patient presents with an unexplained neurological phenotype, such as mild hemiparesis, even in the absence of porencephaly.
Subject(s)
Collagen Type IV/genetics , Epilepsy/genetics , Epilepsy/surgery , Hemispherectomy , Mutation , Brain/diagnostic imaging , Brain/physiopathology , Brain/surgery , Child, Preschool , Epilepsy/diagnostic imaging , Epilepsy/physiopathology , Female , Humans , Treatment OutcomeABSTRACT
BACKGROUND: Congenital cytomegalovirus (CMV) infection causes various neurological sequelae. However, most infected infants are asymptomatic at birth, and retrospective diagnosis is difficult beyond the neonatal period. OBJECTIVE: This study aimed to investigate the aspects of neurological sequelae associated with asymptomatic congenital CMV infection. METHODS: We retrospectively analyzed 182 patients who were suspected of having asymptomatic congenital CMV infection with neurological symptoms in Japan. Congenital CMV infection was diagnosed by quantitative polymerase chain reaction amplification of CMV from dried umbilical cord DNA. RESULTS: Fifty-nine patients (32.4%) who tested positive for CMV were confirmed as having congenital CMV infection. Among 54 congenital CMV patients, major neurological symptoms included intellectual disability (n=51, 94.4%), hearing impairment (n=36, 66.7%) and cerebral palsy (n=21, 38.9%), while microcephaly (n=16, 29.6%) and epilepsy (n=14, 25.9%) were less common. In a brain magnetic resonance imaging (MRI) study, cortical dysplasia was observed in 27 CMV-positive patients (50.0%), and all patients (100%) had cerebral white matter (WM) abnormality. Intracranial calcification was detected by CT in 16 (48.5%) of 33 CMV-positive patients. Cerebral palsy, cortical dysplasia and a WM abnormality with a diffuse pattern were associated with marked intellectual disability. CONCLUSIONS: Brain MRI investigations are important for making a diagnosis and formulating an intellectual prognosis. Analysis of umbilical cord tissue represents a unique and useful way to retrospectively diagnose congenital CMV infection.
Subject(s)
Asymptomatic Infections , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Adolescent , Adult , Brain/diagnostic imaging , Cerebral Palsy/diagnosis , Cerebral Palsy/epidemiology , Cerebral Palsy/physiopathology , Child , Child, Preschool , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/epidemiology , Epilepsy/diagnosis , Epilepsy/epidemiology , Epilepsy/physiopathology , Humans , Infant , Infant, Newborn , Intellectual Disability/diagnosis , Intellectual Disability/epidemiology , Intellectual Disability/physiopathology , Magnetic Resonance Imaging , Malformations of Cortical Development/diagnosis , Malformations of Cortical Development/epidemiology , Malformations of Cortical Development/physiopathology , Polymerase Chain Reaction , Retrospective Studies , Tissue Preservation , Umbilical Cord/microbiology , White Matter/diagnostic imaging , Young AdultABSTRACT
We conducted a [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) study in five patients (median age 11 (range 4-13) years) with Leigh syndrome to evaluate its usefulness for understanding the functional brain dysfunction in this disease and in future drug trials. Four patients were found to have reported mitochondrial DNA gene mutations. The brain T2-weighted magnetic resonance imaging (MRI) showed high-intensity areas in the putamen bilaterally in five patients, caudate bilaterally in four, thalamus bilaterally in two, and brainstem in one. Cerebellar atrophy was observed in older two patients. For disease control, seven age-matched epilepsy patients who had normal MRI and FDG-PET studies were selected. For semiquantitative analysis of the lesions with decreased (18)F-FDG uptake, the mean standard uptake value (SUV) was calculated in regions of interest (ROIs) placed in each brain structure. We compared the SUV of nine segments (the frontal, temporal, parietal, and occipital lobes, thalami, basal ganglia, mid-brain, pons, and cerebellum) between patients with Leigh syndrome and controls. The glucose uptake was decreased significantly in the cerebellum and basal ganglia, which could explain the ataxia and dystonia in patients with Leigh syndrome. Although this study had some limitations, FDG-PET might be useful for evaluating the brain dysfunction and treatment efficacy of new drugs in patients with Leigh syndrome. Further study with more patients using advanced methods to quantify glucose uptake is needed before drawing a conclusion.
Subject(s)
Basal Ganglia/diagnostic imaging , Cerebellum/diagnostic imaging , Fluorodeoxyglucose F18/metabolism , Leigh Disease/diagnostic imaging , Positron-Emission Tomography , Adolescent , Child , Child, Preschool , HumansABSTRACT
Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by prolonged severe seizures and a high-grade fever. We experienced a boy with severe AERRPS with frequent partial seizures that exhibited right-side predominance. The patient required the continuous intravenous administration of many antiepileptic drugs and respirator management for several months. Methylprednisolone pulse therapy and intravenous immunoglobulin administration were only temporarily effective. The MRI and EEG showed the abnormality in the left occipital lobe. Although occipital lobectomy was performed, his seizures continued. His cerebrospinal fluid exhibited elevated protein and proinflammatory cytokine levels, and was positive for anti-glutamate receptor ε2 antibodies. Pathological examination showed infiltration of many neutrophilic leukocytes, T cells, and microglia in the area exhibiting severe spongiosis. We thought that the exaggerated microglia and T-cell responses were related to the pathogenesis of the patient's seizures, and we therefore initiated treatment with tacrolimus. As a result, many of the daily seizure clusters were ameliorated, and the patient was discharged. We attempted to discontinue the tacrolimus twice, but the patient's seizure clusters recurred each time. This is the first case report of the pathological findings of AERRPS and showing an effective therapeutic approach using tacrolimus. Tacrolimus may be an effective immunosuppressant, especially for patients with severe AERRPS.
Subject(s)
Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/drug therapy , Encephalitis/drug therapy , Epilepsies, Partial/drug therapy , Seizures, Febrile/drug therapy , Tacrolimus/therapeutic use , Acute Disease , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Child , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/pathology , Drug Resistant Epilepsy/physiopathology , Electroencephalography , Encephalitis/diagnostic imaging , Encephalitis/pathology , Encephalitis/physiopathology , Epilepsies, Partial/diagnostic imaging , Epilepsies, Partial/pathology , Epilepsies, Partial/physiopathology , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Male , Seizures, Febrile/diagnostic imaging , Seizures, Febrile/pathology , Seizures, Febrile/physiopathologyABSTRACT
OBJECTIVE: GABRA1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA1 mutations. METHODS: In total, 526 and 145 patients with infantile epilepsy were analyzed by whole-exome sequencing and GABRA1-targeted resequencing, respectively. RESULTS: We identified five de novo missense GABRA1 mutations in six unrelated patients. A p.R112Q mutation in the long extracellular N-terminus was identified in a patient with infantile epilepsy; p.P260L, p.M263T, and p.M263I in transmembrane spanning domain 1 (TM1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM2 was identified in a patient with unclassified early onset epileptic encephalopathy. Four of these mutations have not been observed previously. SIGNIFICANCE: Our study suggests that de novo GABRA1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.
Subject(s)
Mutation, Missense/genetics , Receptors, GABA-A/genetics , Spasms, Infantile/diagnosis , Spasms, Infantile/genetics , Amino Acid Sequence , Child , Child, Preschool , Electroencephalography , Female , Humans , Infant , Male , Molecular Sequence Data , Spasms, Infantile/physiopathologyABSTRACT
PURPOSE: This study was aimed to determine what preoperative profiles were associated with seizure remission after corpus callosotomy and whether such seizure outcome was associated with the postoperative developmental outcome. METHODS: This retrospective study included 26 consecutive patients with childhood onset epilepsy who underwent one-stage total corpus callosotomy at our institution and were followed up for a minimum of 1 year. The age at surgery ranged from 13 months to 32 years (median 6 years). The association between postoperative seizure freedom and preoperative profiles, post-operative developmental gains was examined. RESULTS: Five patients achieved seizure freedom (Engel class I), and 10 patients achieved worthwhile reduction of seizures (class III), whereas the remaining patients had a class IV outcome. All five seizure-free patients had "lack of abnormal magnetic resonance imaging findings", "lack of proven etiology of seizures", and underwent "surgery at age 6 years or younger". These three factors were associated with seizure freedom (p<0.05, Fisher exact test). Post-operative gains in developmental quotient were significantly better in patients with seizure freedom than in those without (p<0.05, Mann Whitney U test). CONCLUSION: Our study replicated the notion that seizure remission can be achieved after total corpus callosotomy in subsets of patients with medically-uncontrolled epilepsy, and suggested that a better developmental outcome can be expected in patients benefiting from seizure freedom.
Subject(s)
Corpus Callosum/surgery , Drug Resistant Epilepsy/surgery , Epilepsy, Generalized/surgery , Seizures/surgery , Adolescent , Adult , Child , Child Development , Child, Preschool , Drug Resistant Epilepsy/pathology , Drug Resistant Epilepsy/physiopathology , Epilepsy, Generalized/pathology , Epilepsy, Generalized/physiopathology , Female , Follow-Up Studies , Humans , Infant , Male , Neurosurgical Procedures , Retrospective Studies , Seizures/pathology , Seizures/physiopathology , Treatment Outcome , Young AdultABSTRACT
We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16 years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24 years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome.
Subject(s)
Cerebellar Neoplasms/genetics , Hemangioblastoma/genetics , Chromosome Deletion , Chromosomes, Human, Pair 3/genetics , Comparative Genomic Hybridization , Female , Humans , Young Adult , von Hippel-Lindau DiseaseABSTRACT
Neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative lysosomal diseases. Fourteen distinct NCL subtypes (CLN1-CLN14) are known, and they are caused by mutations in different genes. CLN8 was first identified in Finnish patients, and the phenotype was subsequently found in Turkish, Italian, and Pakistani patients. We report a 6-year-old Japanese boy with NCL with a novel missense mutation in CLN8. At the age of 3years, he manifested frequent drop seizures, and then progressively developed motor difficulties with an ataxic gait, myoclonus, left conjugate deviation, and rotational nystagmus. At age 5, he developed profound visual difficulty and dysphagia, and he has now lost his mobility. A bone marrow examination at age 5 showed sea-blue histiocytes. An electroretinogram was non-recordable. No giant somatosensory evoked potentials were found. Brain magnetic resonance imaging revealed bilateral diffuse hyperintensities in the white matter around the lateral ventricles and cerebellar and pontine atrophy on T2-weighted images. In a lysosomal enzyme study, the palmitoyl-protein-thioesterase and pepinase activity was within normal limits. Whole-exome sequencing revealed a homozygous CLN8 mutation: c.620T>G (p.L207R). His parents were both heterozygous for this mutation. To our knowledge, this is the first report of a CLN8 mutation in late infantile NCL in Japan.