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PubMed2000

Spinal anesthesia in MELAS syndrome: a case with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is one of the classic mitochondrial encephalomyopathies with variable clinical presentation and multisystem involvement. Enhanced sensitivity to neuromuscular blockade or anesthetic agents and susceptibility to malignant hyperthermia in these patients have ever been reported, all of which complicate the management of general anesthesia. To avoid these appalling troubles in general anesthesia, we chose spinal anesthesia for a patient with MELAS syndrome receiving appendectomy. The patient obtained adequate anesthesia and good recovery without neurologic sequelae. Although there is little information about the application of regional anesthesia in MELAS patients, we demonstrate that it may be a satisfactory choice. However, it is suggested that regional anesthesia is performed only when neurological abnormalities of spinal cord or peripheral nerves are definitely ruled out.

Adult↗
PubMed1993

Ophthalmologic manifestations in MELAS syndrome.

We describe a 15-year-old boy with full-blown mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO). He presented with visual disturbance, hearing impairment, continuous partial epilepsy on the right aspect of the face, and right hemiparesis since the age of 13. Four months later, he experienced another strokelike episode with continuous partial epilepsy on the left hand. Serial computed tomographic scans revealed bilateral parieto-occipital hypodense lesions with gyral enhancement and an additional low-density lesion in the right frontal area 4 months later, respectively. Results of laboratory examinations disclosed lactic acidosis and mitochondrial myopathy with many ragged-red fibers. To identify the defective gene in mitochondrial DNA, a simple molecular test was performed by using restriction endonuclease Apa I. A transition from A to G was found at nucleotide position 3243 of the tRNA(Leu) gene. Interestingly, the patient also had marked external ophthalmoplegia and ptosis commonly found in patients with CPEO. Therefore, we suggest that ophthalmoplegia also occurs in the MELAS syndrome.

Adolescent↗
PubMed1994

[MELAS syndrome. Clinical aspects, MRI, biochemistry and molecular genetics].

MELAS is a mitochondrial cytopathy characterized by encephalopathy with stroke-like episodes and lactic acidosis. Most patients exhibit an A-G transition mutation at np 3243 of mitochondrial DNA (tRNA(Leu)(UUR)). We present a family of four in which the mutation was discovered in blood and in muscle mt DNA. Two patients had the classic MELAS syndrome with multiple stroke-like episodes. Some episodes were precipitated by metabolic stress. The remaining two patients had an oligosymptomatic disease with mild chronic encephalopathy, small stature and hearing loss. MRI was followed over a period of 4-8 years, during which the MELAS patients showed progression from nonspecific multifocal signal change to typical extensive cortico-subcortical parieto-occipital lesions and progressive cerebral atrophy. MRI in the oligosymptomatic cases was normal, or showed non-progressive cerebellar atrophy. Biochemical findings were non-specific, indicating increased mitochondrial volume in all cases, and a relatively complex IV defect in one case. All patients were treated with coenzyme Q with varying clinical response. The percentage of mutant mt DNA in blood and muscle did not correlate with clinical severity. Pathogenetic theories based on molecular genetics, and the therapeutic regimen in terms of the underlying biochemical concepts are discussed.

Adolescent↗
PubMed2000

Invasive aspergillosis in a patient with MELAS syndrome.

Invasive infection with the opportunistic fungus Aspergillus fumigatus predominantly affects people with impaired cell mediated immunity. The case of a 31 year old woman with no identified cause for immunosuppression who presented with severe refractory aspergillosis of the paranasal sinuses is reported. She subsequently developed clinical and molecular evidence of mitochondrial encephalomyopathy with lactic acidosis and stroke-like events (MELAS) syndrome. It is proposed that MELAS syndrome may represent an unusual risk factor for the development of invasive aspergillosis and mechanisms are supported by which mitochondrial dysfunction may predispose to this.

Adult↗
PubMed1997

Sensorineural hearing loss in MELAS syndrome.

A case of sensorineural hearing loss (SNHL) in MELAS syndrome, a variety of mitochondrial cytopathy, is presented. Mitochondrial cytopathies have gone almost unreported in the otolaryngology literature, despite evidence from a recent review that about 60 per cent of such patients suffer from SNHL (Gold and Rapin, 1994). The same review revealed that only one of 117 case reports in the period 1984-1993 contained an audiogram (Swift and Singh, 1988), and none presented sequential audiograms. However, audiometry has since been published on 23 members of a family with a mitochondrial point mutation causing only sensorineural hearing loss with no other symptoms (Vernham et al., 1994). We present a case of mitochondrial cytopathy three years after diagnosis with two sequential audiograms.

Adult↗
PubMed2002

Spinal dysraphism associated with congenital heart disorder in a girl with MELAS syndrome and point mutation at mitochondrial DNA nucleotide 3271.

We describe a case of mitochondrial encephalopathy, lactacidosis, and stroke-like episode (MELAS syndrome) associated with ventricular septal defect and meningocele at the L3 level in a 5-year-old girl. Mitochondrial DNA analysis showed point mutation at nucleotide 3271--> TC. The occurrence of heart and neural tube defects in association with usual features of the MELAS syndrome might be explained by either defective high-energy metabolism during early embryogenesis or a common genetic cause.

Child↗
PubMed1993

MELAS syndrome masquerading as herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) is commonly treated empirically with acyclovir without confirmatory brain biopsy. Three consecutive adults with molecularly verified mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presented with, and were treated for, apparent HSE. MELAS syndrome in adults may present as an atypical, recurrent form of HSE and should be added to the list of neurologic diseases that can mimic HSE.

Adolescent↗
PubMed2000

Cerebral blood flow, vascular response and metabolism in patients with MELAS syndrome--xenon CT and PET study.

UNLABELLED: Two patients with MELAS syndrome underwent serial measurement of cerebral blood flow (CBF) with xenon CT while they were presenting stroke like episodes accompanying cerebral lesion detectable with CT. One of them underwent PET measurement of regional cerebral metabolic rate of oxygen (CMRO2) and glucose (CMRGlu) after his symptoms and lesion disappeared. METHODS: The xenon CT CBF study was performed by 4 min wash-in and 3 min wash-out protocol with serial measurement of endexpiratory concentration of xenon gas. The CBF after acetazolamide loading was also quantified in one of them. The PET study was performed to quantify CBF, CMRO2, oxygen extraction fraction (OEF) and cerebral blood volume (CBV) by continuous inhalation of O-15 labeled gases and arterial blood sampling. The PET measurement of CMRGlu was performed by i.v. injection of F-18 FDG and arterial blood sampling. RESULTS: 1) During the symptomatic period, Xe-CBF was normal or slightly increased both in and outside the low density lesion. 2) The CBF response to acetazolamide loading was well preserved both in and outside the low density lesions. 3) After the neurological symptoms and low density lesions disappeared, Xe-CBF pattern and vascular response was the same as during the symptomatic period. 4) In the PET study, normal or slightly increased PET-CBF, increased CMRGlu and markedly decreased CMRO2 in comparison to normal control was noted resulting in a marked decrease in OEF and CMRO2/CMRGlu ratio, a characteristic metabolic pattern for MELAS. CONCLUSION: In the present cases, resting CBF and vasomotor reactivity was well preserved both in symptomatic and remission period. On the contrary, abnormal metabolic pattern was noted. The stroke like episode of the present patients is more likely attributed to metabolic failure than vascular accident.

Adult↗
PubMed1999

Successful cochlear implantation in a patient with MELAS syndrome.

OBJECTIVE: To describe methods of assessing cochlear implant candidacy in patients with potentially significant peripheral and central nervous system (CNS) degeneration. STUDY DESIGN: A patient with a degenerative CNS disease (MELAS syndrome) undergoing evaluation for cochlear implantation is described. SETTING: This study took place at a tertiary care center. PATIENT: A patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who had cortical blindness and profound sensorineural hearing loss was evaluated and rehabilitated with cochlear implantation. INTERVENTIONS: Pure-tone audiogram, behavioral responses to promontory stimulation electrical auditory brainstem response, and electrically evoked middle-latency responses (MLRs) were used to assess eighth nerve, auditory brainstem, and cortical auditory pathways. Cochlear implantation with Cochlear Corporation mini 22 implant was performed. RESULTS: Repeatable electrically evoked MLRs and behavioral responses to promontory stimulation documented the presence of auditory cortical responses. Successful implantation resulted in open set speech recognition and communication using the auditory/oral mode. CONCLUSION: This report describes successful implantation in a patient with MELAS syndrome and demonstrates the ability to preoperatively confirm the integrity of brainstem and cortical auditory pathways despite significant CNS degeneration.

Adult↗
PubMed1996

MELAS syndrome associated with a tandem duplication in the D-loop of mitochondrial DNA.

We describe a family with two cases of adult-onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. Interestingly, the proband also had non-insulin dependent diabetes mellitus and hyperthyroidism. Endocrinological studies demonstrated a high titer of TSH receptor antibody in the proband and elevated levels in her maternal relatives. Analysis of mitochondrial DNA (mtDNA) showed an A-to-G transition at nucleotide position 3243 in the tRNA (Leu(UUR)) gene (A3243G) in the three generations of the family. Furthermore, a previously described -260 bp tandem duplication in the D-loop region of mtDNA was also found in the proband and her maternal relatives. To our knowledge, such kind of duplication has never before been reported in the MELAS syndrome. The proportions of mtDNA with the -260 bp tandem duplication and A3243G point mutation were 12.5% and 82% in the muscle, respectively, and 1.6% and 35% in the blood cells, respectively, of the proband. We conclude that the hyperthyroidism in this MELAS patient may be related to the tandem duplication in the D-loop of mtDNA. This study further substantiates the importance of searching for additional genetic mutations in mitochondrial encephalomyopathic patients with new clinical phenotypes.

Adult↗
PubMed1987

Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome.

Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1-14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase.

Acidosis, Lactic↗
PubMed1993

Ocular pathology of MELAS syndrome with mitochondrial DNA nucleotide 3243 point mutation.

PURPOSE: The authors describe the clinical, histopathologic, and ultrastructural findings in two eyes obtained at autopsy from a 21-year-old woman with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome). METHODS: The eyes were obtained immediately after death. The right eye was fixed in 10% neutral-buffered formalin and processed for standard histologic examination. The left eye was fixed in a neutral-buffered 2.5% glutaraldehyde solution and processed for transmission electron microscopic examination. The authors compared the histologic and ultrastructural findings with the clinical features recorded photographically. RESULTS: The main clinical ophthalmologic features were bilateral ptosis, chronic external ophthalmoplegia, diffuse choroidal atrophy, atypical pigmentary retinopathy with macular involvement, and patchy atrophy of the iris stroma. Molecular genetic analysis detected a tRNA Leu (UUR) point mutation at position 3243 of mitochondrial DNA (MELAS genotype). Results of histologic and ultrastructural examination showed ragged-red fibers in the rectus muscles, degeneration of photoreceptor outer segments in the macula, hyperpigmentation and atrophy of the retinal pigment epithelium of the macula, atrophy of the iris stroma, early posterior subcapsular cataract, and optic atrophy. The retinal pigment epithelium, inner segments of the photoreceptors, smooth muscle cells of the choroidal and retinal vessels, the dilator and sphincter muscle of the iris, cornea, lens epithelium, and ciliary epithelium all contained many, often enlarged, structurally abnormal mitochondria with occasional paracrystalline inclusions and circular cristae. CONCLUSIONS: The MELAS-associated mitochondrial DNA nucleotide 3243 point mutation can cause a spectrum of ocular signs and symptoms that may be dependent on the patient's age and the amount of mutant mitochondrial DNA in the tissue. MELAS syndrome should be considered in the differential diagnosis of bilateral ptosis, external ophthalmoplegia, and atypical pigmentary retinopathy with macular involvement.

Adult↗
PubMedDate not supplied

A novel mutation in the mitochondrial 16S rRNA gene in a patient with MELAS syndrome, diabetes mellitus, hyperthyroidism and cardiomyopathy.

Using RNase protection analysis, we found a novel C to G mutation at nucleotide position 3093 of mitochondrial DNA (mtDNA) in a previously reported 35-year-old woman exhibiting clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome together with diabetes mellitus, hyperthyroidism and cardiomyopathy. The patient also had an A3243G mutation in the tRNA(Leu(UUR)) gene and a 260-base pair duplication in the D-loop of mtDNA. The fibroblasts of the patient were cultured and used for the construction of cybrids using cytoplasmic transfer of the patient's mtDNA to the mtDNA-less rho(0) cells. RNA isolated from the cybrids was subjected to RNase protection analysis, and a C3093G transversion at the 16S rRNA gene and a MELAS-associated A3243G mutation of mtDNA were detected. The novel C3093G mutation together with the A3243G transition were found in muscle biopsies, hair follicles and blood cells of this patient and also in her skin fibroblasts and cybrids. The proportion of the C3093G mutant mtDNA in muscle biopsies of the patient was 51%. In contrast, the mutation was not detected in three sons of the proband. To characterize the impact of the mtDNA mutation-associated defects on mitochondrial function, we determined the respiratory enzyme activities of the primary culture of fibroblasts established from the proband, her mother and her three sons. The proportions of mtDNA with the C3093G transversion and the A3243G transition in the fibroblasts of the proband were 45 and 58%, respectively. However, the fibroblasts of the proband's mother and children harbored lower levels of mtDNA with the A3243G mutation but did not contain the C3093G mutation. The complex I activity in the proband's fibroblasts was decreased to 47% of the control but those of the fibroblasts of the mother and three sons of the proband were not significantly changed. These findings suggest that the C3093G transversion together with the A3243G transition of mtDNA impaired the respiratory function of mitochondria and caused the atypical MELAS syndrome associated with diabetes mellitus, hyperthyroidism and cardiomyopathy in this patient.

Adult↗
PubMedDate not supplied

N-isopropyl-p-[123I]iodoamphetamine SPECT in MELAS syndrome: comparison with CT and MR imaging.

Regional cerebral perfusion was studied in three patients with the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, using single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP). Accumulation of the tracer was relatively decreased in the parietooccipital regions and also in the frontotemporal regions after stroke-like episodes. However, quantitative regional cerebral blood flow (rCBF) measurement showed that rCBF was relatively well preserved even at these sites, and a hyperemic state was observed at the sites of normal accumulation. IMP SPECT may be useful in the diagnosis and assessment of the progress of the MELAS syndrome.

Acidosis, Lactic↗
PubMed2000

Absence of maternal A3243G mtDNA mutation and reversible hyperglycemia in a patient with MELAS syndrome.

We report the unusual features of a female patient who had MELAS-specific A3243G mutation in mitochondrial DNA (mtDNA) and diabetes mellitus (DM). The patient showed mitochondrial myopathy, encephalopathy, lactic acidosis, and deafness but lacked the stroke-like episode. Acute hyperglycemia was noted after one attack of status epilepticus. Molecular genetic analysis demonstrated a heteroplasmic A3243G point mutation in the mtDNAs of muscle, blood cells and hair follicles. Glucagon stimulation test exhibited marked depression of pancreatic beta-cell function. However, in a further study neither this mutation, nor MELAS syndrome or DM, was found in all of her maternal relatives. A series of follow-up studies for beta-cell function also showed gradual improvement. The pedigree study led us to believe that this A3243G mutation arose from the germ line cells or occurred later in somatic tissues of the patient. We also suggest that the A3243G mutation of mtDNA may elicit the pathogenesis of a subtype of DM. Nevertheless, environmental stress may be another important factor for provocation of the disease.

Adult↗
PubMed1995

MELAS syndrome: peripheral neuropathy and cytochrome C-oxidase deficiency: a case report and review of the literature.

A 4-year-old boy presented with developmental delay, aggressive behavior, and incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and lactic acidemia following exercise were noted. Electromyography was myopathic and nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy demonstrated variation in fiber size and an excess of lipid droplets. He than had several stroke-like episodes and periods of unconsciousness, associated with severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This boy displayed the classical clinical and biochemical features of MELAS syndrome, namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin, coenzyme Q10, and corticosteroids. He died at the age of 14 years following an episode of seizures, coma, and gastrointestinal hemorrhage. This is the first reported case of MELAS syndrome in Israel.

Child, Preschool↗
PubMed1998

[MELAS syndrome in a five year-old child: clinical, biological and genetic characteristics].

BACKGROUND: MELAS syndrome is a rare mitochondrial cytopathy; its diagnosis can be difficult. CASE REPORT: A 6-month-old boy presented with febrile seizures, possibly due to viral meningitis. At 7 months, he developed myoclonia and "brain attacks" and, subsequently, myoclonical attacks, regression of psychomotor and mental acquisitions, and progressive visual loss. The ratio of lactatorachia/lactacidemia was increased. The molecular genetic analysis showed an heteroplasmic point mutation with A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(leu) (UUR) gene. He was the second child of a mother having frequent headaches. His great aunt, a sister of his maternal grandmother, was mentally retarded and had frequent epileptic seizures and hemiparesy since her childhood. CONCLUSION: Any unusual neurological symptom, particularly when combined with "illegitimate" symptoms, should lead to search for a mitochondrial cytopathy.

Child, Preschool↗
PubMedDate not supplied

[MELAS syndrome: clinical, pathological and neuroimaging study].

The form of presentation of a new case of Melas Syndrome is described, together with a pathological and neuroimage study, including clinical development over a 3 year period. The usefulness of MR should be underlined here, given clinical doubts, and also normality in the EMG early phases of and the association with obstructive hypertrophic miocardiopathy.

Adolescent↗