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We report on a patient with delayed post-hypoxic leukoencephalopathy (DPHL) who showed akinetic mutism and gait disturbance, neural injuries that were demonstrated on diffusion tensor tractography (DTT). A patient was exposed to carbon monoxide (CO) and rapidly recovered; however, two weeks after onset, he began to show cognitive impairment and gait disturbance. At six weeks after CO exposure, he showed akinetic mutism and gait inability. DTT at 6-weeks post-exposure showed discontinuations in neural connectivities of the caudate nucleus to the medial prefrontal and orbitofrontal cortex in both hemispheres. In addition, the corticoreticulospinal tract revealed severe thinning in both hemispheres.
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Mutismo Acinético , Imagen de Difusión Tensora , Trastornos Neurológicos de la Marcha , Leucoencefalopatías , Humanos , Mutismo Acinético/etiología , Mutismo Acinético/fisiopatología , Masculino , Leucoencefalopatías/etiología , Leucoencefalopatías/fisiopatología , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Hipoxia Encefálica/complicaciones , Hipoxia Encefálica/diagnóstico por imagen , Persona de Mediana Edad , AdultoRESUMEN
Labrune syndrome is an uncommon central nervous system disorder characterized by leukoencephalopathy, cerebral calcifications, and cysts on brain imaging. The basic pathology is microangiopathy resulting from a mutation in the SNORD118 gene. Radiological imaging is the hallmark of the disease.
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Calcinosis , Quistes , Leucoencefalopatías , Humanos , Calcinosis/diagnóstico por imagen , Calcinosis/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/genética , Leucoencefalopatías/complicaciones , Quistes/diagnóstico por imagen , Quistes/complicaciones , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Masculino , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/genética , Femenino , Tomografía Computarizada por Rayos X , ARN Nucleolar Pequeño/genéticaAsunto(s)
Leucoencefalopatías , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/genética , Leucoencefalopatías/complicaciones , Masculino , Imagen por Resonancia Magnética , CADASIL/complicaciones , CADASIL/diagnóstico por imagen , CADASIL/genética , Femenino , Persona de Mediana Edad , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/etiología , Puente/diagnóstico por imagen , Puente/patologíaRESUMEN
INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one kind of monogenic hereditary small-vessel disease in the brain caused by mutations in the NOTCH3 gene. However, it is rare for CADASIL to recur with different clinical manifestations in 1 patient, and some atypical clinical manifestations can easily lead to misdiagnosis by clinical physicians. CASE CONCERN: A 34-year-old male presented with transient speech disorder accompanied by weakness in the left side of the body for 1 day in June 2020. Magnetic resonance imaging showed acute ischemic infarction in right centrum semiovale, along with multiple abnormal white matter hyperintensities in the brain. Genetic sequencing identified a heterozygous mutation in the NOTCH3 gene. The patient experienced recurrent episodes in 2021 and 2023, with varying clinical symptoms including visual blurring, abnormal limb sensation, and sudden cognitive dysfunction. DIAGNOSIS: The diagnoses of CADASIL is based on clinical manifestations, imaging results, and genetic reports. INTERVISION AND OUTCOMES: The patient was received symptomatic treatment including antiplatelet aggregation therapy, lipid regulation, and plaque stabilization, resulting in improved symptoms. OUTCOMES: During the course of the disease, after medication treatment and rehabilitation exercise, the patient clinical symptoms have significantly improved. Currently, the patient is closely following up and regularly undergoing relevant examinations. LESSONS: In this rare case, we found that CADASIL can recur multiple times in a patient with different clinical symptoms, which can easily lead to clinical misdiagnosis. Clinicians should consider the possibility of CADASIL in young patients with sudden typical neurological dysfunction.
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CADASIL , Leucoencefalopatías , Masculino , Humanos , Adulto , CADASIL/complicaciones , CADASIL/diagnóstico , CADASIL/genética , Receptor Notch3/genética , Encéfalo/patología , Mutación , Imagen por Resonancia Magnética , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/patologíaRESUMEN
BACKGROUND: The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. METHODS: We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94â567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. FINDINGS: From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86-1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47-4·74; p=0·0013 vs 3·41, 1·91-6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23-7·19 vs 3·94, 1·95-7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04-2·94 vs 0·68, 0·39-1·20; pdiff=0·023). INTERPRETATION: The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. FUNDING: National Institute for Health and Care Research and Wellcome Trust.
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Delirio , Demencia , Ataque Isquémico Transitorio , Leucoencefalopatías , Accidente Cerebrovascular , Estados Unidos , Humanos , Masculino , Femenino , Anciano , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Encéfalo/diagnóstico por imagen , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/epidemiología , Leucoencefalopatías/complicaciones , Demencia/diagnóstico por imagen , Demencia/epidemiología , Demencia/etiología , Delirio/diagnóstico por imagen , Delirio/epidemiología , Delirio/etiologíaRESUMEN
A patient in her 50s presented with altered mental status and shortness of breath at 4600 m elevation. After descent to the base of the mountain, the patient became comatose. She was found to have bilateral pulmonary infiltrates and a serum sodium of 102 mEq/L. She was rapidly corrected to 131 mEq/L in 1 day. Initial MRI showed intensities in bilateral hippocampi, temporal cortex and insula. A repeat MRI 17 days post injury showed worsened intensities in the bilateral occipital lobes. On admission to acute rehabilitation, the patient presented with blindness, agitation, hallucinations and an inability to follow commands. Midway through her rehabilitation course, antioxidant supplementations were started with significant improvement in function. Rapid correction of hyponatraemia may cause central pontine myelinolysis or extrapontine myelinolysis (EPM). In some cases of hypoxic brain injury, delayed post-hypoxic leucoencephalopathy (DPHL) may occur. Treatment options for both disorders are generally supportive. This report represents the only documented interdisciplinary approach to treatment of a patient with DPHL and EPM. Antioxidant supplementation may be beneficial as a treatment option for both EPM and DPHL.
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Lesiones Encefálicas , Hiponatremia , Leucoencefalopatías , Mielinólisis Pontino Central , Femenino , Humanos , Antioxidantes/uso terapéutico , Mielinólisis Pontino Central/complicaciones , Hiponatremia/etiología , Lesiones Encefálicas/complicaciones , Hipoxia/complicaciones , Leucoencefalopatías/complicaciones , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Mutations in type IV collagen gene COL4A1 are identified as a cause of autosomal dominant cerebrovascular disease. We report an unusual late-onset presentation. CASE REPORT: A 64-year-old male was found to have an ischemic stroke and diffuse white matter changes. Genetic testing revealed COL4A1 gene mutation of heterozygous Alu insertion at intron 16. Alu elements are known as "jumping genes," and Alu insertion is not previously reported in COL4A1 genetic syndromes. Our case has attributes consistent with a heritable leukoencephalopathy: (1) late-onset presentation, (2) intracerebral hemorrhages and microbleeds, (3) bilateral symmetrical leukoencephalopathy, (4) recurrence over a short period of time, (5) bilateral retinopathy, and (6) family history notable for brain aneurysm, kidney diseases, and early-onset stroke. CONCLUSIONS: Although the majority of COL4A1 genetic syndromes featuring cerebral small vessel disease are in children, this case highlights a late-onset patient with key features of COL4A1 syndromes associated with a heterozygous Alu intronic insertion.
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Accidente Cerebrovascular Hemorrágico , Leucoencefalopatías , Accidente Cerebrovascular , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Accidente Cerebrovascular Hemorrágico/complicaciones , Leucoencefalopatías/complicaciones , Mutación/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/complicacionesRESUMEN
RATIONALE: Toxic leukoencephalopathy, a condition resulting from exposure to toxic substances, can lead to malignant catatonia, a severe motor dysfunction with symptoms such as muscle rigidity and high-spiking fever, hypertensive urgency, and tachycardia. This case study investigates the relationship between toxic leukoencephalopathy-induced malignant catatonia and heart rate variability (HRV), a marker of autonomic nervous system function. PATIENT CONCERNS: A 51-year-old male presented to the emergency department with acute onset of progressively worsening mental status. DIAGNOSES: The patient was diagnosed with cocaine-induced toxic leukoencephalopathy causing malignant catatonia. INTERVENTIONS: A 5-day escalating treatment regimen was instituted for the management of malignant catatonia until resolution. Daily HRV parameters in the temporal and frequency domain, geometric data, and cardiac entropy were recorded using HRVAnalysis v.1.2 (ANS Lab Tools). The HRV analysis was correlated with pharmacologic management, the Bush-Francis catatonia rating scale, and hemodynamic parameters, including blood pressure, heart rate, and temperature. OUTCOMES: The results showed a correlation between the severity and frequency of malignant catatonic episodes and the patient autonomic dysfunction. Improvement in malignant catatonia with pharmacological management was associated with an improved HRV, including elevated rMSSD, SDNN, cardiac entropy, and pNN50%. LESSONS: Malignant catatonia is associated with decreased HRV, and its management is associated with an increase. This suggests a link between malignant catatonia and autonomic dysfunction, highlighting the potential benefits of treating malignant catatonia to improve autonomic function and reduce cardiovascular risk.
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Catatonia , Leucoencefalopatías , Masculino , Humanos , Persona de Mediana Edad , Catatonia/diagnóstico , Frecuencia Cardíaca , Corazón , Leucoencefalopatías/complicacionesRESUMEN
Methotrexate-induced neurotoxicity is a well-defined side-effect of high-dose and intrathecal methotrexate with characteristic clinico-radiological findings and transient nature. Our experience in managing this entity in children with acute lymphoblastic leukemia(ALL) is reported here. All children with de novo ALLregistered from January 2016 through December 2021 who developed methotrexate-induced neurotoxicity were included. Of children with ALL treated during the study period, thirty-three experienced methotrexate induced neurotoxicity with an incidence of 1.25%. Stroke-like symptoms(36.36%; 12/33) were the most common clinical manifestation followed by seizures(30.3%, 10/33). Twenty-three patients had radiological features consistent with methotrexate-induced leukoencephalopathy. With emerging evidence, thirty-one patients were re-challenged with methotrexate (IV/IT), of whom 4 patients had recurrence of symptoms. No long-term neurological sequalae were noted in our cohort, despite rechallenging. Therefore in our study, methotrexate induced neurotoxicity is a self-limiting toxicity and methotrexate can be re-challenged safely without compromising theintensity of CNS-directed therapy.
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Leucoencefalopatías , Metotrexato , Síndromes de Neurotoxicidad , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Estudios de Seguimiento , Leucoencefalopatías/inducido químicamente , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico , Metotrexato/efectos adversos , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , RadiografíaRESUMEN
A 30-year-old woman developed symptoms, signs and neurophysiology consistent with Guillain-Barré syndrome and was admitted to the neurosciences intensive care unit owing to respiratory compromise. Here, she received a clonidine infusion for agitation, complicated by a minor hypotensive episode, following which she became unconscious. MR scan of the brain showed changes compatible with hypoxic brain injury. Urinary amino acids showed increased urinary α-ketoglutarate. Genetic testing using whole-exome sequencing identified pathogenic variants in the SLC13A3 gene known to be associated with an acute reversible leukoencephalopathy with increased urinary α-ketoglutarate. The case highlights the importance of considering inborn errors of metabolism in cases of unexplained encephalopathy.
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Síndrome de Guillain-Barré , Leucoencefalopatías , Femenino , Humanos , Adulto , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , Ácidos Cetoglutáricos , Leucoencefalopatías/complicaciones , Encéfalo/patología , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: There is an unmet need for the treatment of colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy. OBJECTIVES: To evaluate the association of glucocorticoids (GCs) with disease onset and progression in CSF1R variant carriers. METHODS: Retrospective cohort study on CSF1R variants carriers (n = 41) whose medical records were collected at Mayo Clinic Florida from 2003 to 2023. We retrieved information on sex, ethnicity, family history, medications, disease onset, course and duration, neuroimaging features, and activities of daily living (ADL). RESULTS: Risk of developing symptoms was significantly lower for individuals who used GCs (n = 8) compared to individuals who did not (n = 33) (12.5% vs. 81.8%, hazard ratio [HR] = 0.10, P = 0.036). The risk of becoming dependent in ADL was markedly lower for the GCs group (0.0% vs. 43.8%, P = 0.006). White matter lesions and corpus callosum involvement were less common in the GCs group (62.5% vs. 96.6%, P = 0.026; 37.5% vs. 84.6%, P = 0.017; respectively). CONCLUSIONS: We found a protective association of GCs in CSF1R variant carriers against developing CSF1R-related leukoencephalopathy. We call for further studies to validate our findings and investigate the potential application of GCs in CSF1R-related leukoencephalopathy. © 2023 International Parkinson and Movement Disorder Society.
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Glucocorticoides , Leucoencefalopatías , Humanos , Glucocorticoides/uso terapéutico , Estudios Retrospectivos , Actividades Cotidianas , Mutación , Leucoencefalopatías/complicacionesRESUMEN
OBJECTIVES: Phenylketonuria (PKU) is the most prevalent congenital disease of amino acid metabolism. Neurological manifestations usually complicate PKU in untreated adult patients. This study describes neurological and imaging phenotypes of adult patients with untreated PKU. METHODS: We investigated a cohort of 320 unrelated adult patients with suspected genetic leukoencephalopathies using whole-exome sequencing (WES). We analyzed the phenotypic features of adult PKU patients in our cohort and summarized cases reported in the literature. RESULTS: We identified 10 patients in our cohort and 12 patients in the literature, who presented with neurological manifestations and were diagnosed with PKU in adulthood. Approximately 60% of these patients had onset of clinical features in adulthood. The most common neurological symptoms of patients presenting in adulthood were cognitive disturbance and spastic paralysis, followed by vision loss, cerebellar ataxia, weakness of limbs, and seizure. This differed from that of patients presenting with PKU features in childhood, who consistently had mental retardation with various neurological complications emerging during a broad age range. Imaging findings were similar between patients presenting with clinical features in childhood compared with adulthood, comprising symmetric periventricular white matter hyperintense on T2-weighted imaging and diffusion-weighted imaging predominantly in the parietal and occipital lobes. Also, normal brain imaging and diffuse leukoencephalopathies were observed in both patient groups. CONCLUSION: PKU with clinical features presenting in adulthood is an atypical subtype and should be considered during diagnosis of adults with neurological symptoms and leukoencephalopathy. DWI seems to be most helpful to distinguish patients with PKU. Additionally, we demonstrate that PKU constitutes a part (3.1%) of adult genetic leukoencephalopathies.
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Leucoencefalopatías , Fenilcetonurias , Humanos , Fenilcetonurias/complicaciones , Fenilcetonurias/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Leucoencefalopatías/complicaciones , Convulsiones , FenotipoRESUMEN
RATIONALE: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain. PATIENT CONCERNS: Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale. DIAGNOSES: Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension. INTERVENTIONS: Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up. OUTCOMES: No further seizures were recorded and the patient recovered well. LESSONS: MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.
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Acidosis Láctica , Leucoencefalopatías , Síndrome MELAS , Accidente Cerebrovascular , Masculino , Femenino , Humanos , Persona de Mediana Edad , Acidosis Láctica/complicaciones , Síndrome MELAS/complicaciones , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Levetiracetam/uso terapéutico , Midazolam/uso terapéutico , Accidente Cerebrovascular/etiología , Ácido Ascórbico/uso terapéutico , Vitaminas/uso terapéutico , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico , Vitamina E/uso terapéuticoRESUMEN
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a well-known mitochondrial depletion syndrome. Since Van Goethem et al. described MNGIE syndrome with pathogenic POLG1 mutations in 2003, POLG1 gene became a target for MNGIE patients. Cases with POLG1 mutations strikingly differ from classic MNGIE patients due to a lack of leukoencephalopathy. Here we present a female patient with very early onset disease and leukoencephalopathy compatible with classic MNGIE disease who turned out to have homozygous POLG1 mutation compatible with MNGIE-like syndrome, mitochondrial depletion syndrome type 4b.
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Leucoencefalopatías , Encefalomiopatías Mitocondriales , Humanos , Femenino , Encefalomiopatías Mitocondriales/complicaciones , Encefalomiopatías Mitocondriales/genética , Encefalomiopatías Mitocondriales/patología , Timidina Fosforilasa/genética , Mutación/genética , Leucoencefalopatías/genética , Leucoencefalopatías/complicaciones , SíndromeRESUMEN
Leukoencephalopathy with calcifications and cysts (LCC; OMIM #614561) is a rare disease and at present there are less than 100 cases reported worldwide. Mutations in the SNORD118 gene is now known to be the cause of LCC. We present a case who was heterozygous for the n.70G>A and n.6C>T sequence variants of the SNORD118 gene, variants which to date have not been described. Compared with the cases that we reviewed, our patient had the second longest time to diagnosis (age 56) from onset of symptoms 40 years prior. Moreover, his cousin's family has a high prevalence of epilepsy. This paper reviewed all published reports to date that had descriptive cases involving LCC as well as testing for the SNORD118 gene. Since 1996 only 85 patients have been described in 59 case reports. In this review, we summarize their clinical features, especially central nervous system symptoms, treatment, pathology, and gene testing results.