Abstract:We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS finding… Show more
“…Approximately 67.9% of LHON cases present with high-intensity optic chiasm and bilateral optic tracts on T2-weighted MRI; 12 however, 4.1% to 10% of GC cases also present with such findings. 13–15 Patients with LHON infrequently present with white matter changes on MRI, 10 , 16 , 17 but none so far have presented with diffuse infiltrates, such as the present case.…”
BACKGROUIND
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes.
OBSERVATIONS
The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2′-deoxyguanosine positivity, suggesting the presence of oxidative stress.
LESSONS
LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.
“…Approximately 67.9% of LHON cases present with high-intensity optic chiasm and bilateral optic tracts on T2-weighted MRI; 12 however, 4.1% to 10% of GC cases also present with such findings. 13–15 Patients with LHON infrequently present with white matter changes on MRI, 10 , 16 , 17 but none so far have presented with diffuse infiltrates, such as the present case.…”
BACKGROUIND
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes.
OBSERVATIONS
The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2′-deoxyguanosine positivity, suggesting the presence of oxidative stress.
LESSONS
LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.
“…Furthermore, up-todate diagnostic techniques have allowed for a much earlier detection of the disease (38). Differential diagnosis should be performed in order to rule out other possible causes with similar clinical signs and symptoms (1,39,40).…”
Section: Clinical Characteristics: Children Versus Adultsmentioning
confidence: 99%
“…This class of medication reduces relapses in adults by as much as 30% (6,40). These drugs, with anti-inflammatory and immunomodulatory effects, significantly reduce the frequency and severity of clinical relapses and disease activity, as shown by MRI of the brain, as well as reduce the degree of disability (39). Results for interferon beta-1a application in young children (aged 2-11 years) versus adolescents (aged 12-17 years) have shown that the safety profile is similar.…”
Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). The etiology of MS is most likely multifactorial; it is dependent on genetic, autoimmune, and environmental factors, with a variable course among patients. The two main clinical events that characterize MS are relapses and progression. In recent years, diagnosis and treatment of pediatric MS has drawn attention of the scientific community. Management of pediatric MS focuses on reducing relapses and symptoms via administration of disease-modifying drugs (DMDs) and specific symptomatic treatment. A multidisciplinary approach to pediatric MS treatment is preferred, which aims at alleviating and preventing the accumulation of neurological deficits. MS therapy should be based on DMDs, that is, immunomodulatory drugs. These drugs, which sequester immune system activity, are further subdivided into two categories: first-line and second-line immunomodulatory therapy. First-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b,
Multiple Sclerosis in Pediatric Patients
40and glatiramer acetate) is ineffective (either no response or partial response) in roughly 30% of patients. Patients with a poor response to first-line therapy require second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab, alemtuzumab, and ocrelizumab). In addition to immunomodulatory drugs, treatment of relapses also involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis.
“…The most common diseases that must be taken into account before establishing a definitive diagnosis of MS are presented in Fig. 1 [1, 39, 40]. Fig.…”
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment. The treatment of children with MS has to be multidisciplinary and include pediatric neurologists, ophthalmologists, psychologists, physiotherapists, and if necessary, pediatric psychiatrists and pharmacologists. The basis of MS therapy should rely on drugs that are able to modify the course of the disease, i.e. immunomodulatory drugs. These drugs can be subdivided into two general categories: first-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, glatiramer acetate) and second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab). Treatment of relapses involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. We summarize here the current available information related to the etiology and treatment options in MS. Early administration of immunomodulatory therapy is beneficial in adults, while more studies are needed to prove their effectiveness in pediatric populations. Therefore, pediatric MS still represents a great challenge for both, the early and correct diagnosis, as well as its treatment.
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