Pursuit-paretic and epileptic nystagmus in MELAS

A 27-year-old man with MELAS 3243 mutation developed a right homonymous hemianopia, left beating nystagmus, and impaired smooth pursuit (SP) to the left. Intermittently, the left beating nystagmus changed to right beating with rightward eye and head deviation and associated altered mental status. Each episode lasted several minutes. MRI revealed restricted diffusion in left parieto-temporo-occipital cortices. During the ictus, electroencephalogram showed epileptic discharges in the left temporo-occipital region, and single photon emission computed tomography demonstrated hyperperfusion in the same area. The interictal left beating nystagmus may be ascribed to contralesional bias of SP imbalance since the parieto-temporo-occipital region is involved in the generation of SP. The ictal right beating nystagmus and rightward head and eye deviation indicate coactivation of the SP areas and parietal eye field. This report documents the novel co-occurrence of pursuit-paretic and epileptic nystagmus.     

MELAS syndrome: correlation between clinical features and molecular genetic analysis

The clinical manifestations and mitochondrial DNA (mtDNA) mutations in a Taiwanese family with a female proband exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome are reported. Clinically, the proband had a stroke-like episode with right hemiparesis, hemianopsia and mental dysfunction as well as short stature, hearing impairments, and elevated lactate levels. Brain magnetic resonance images showed multiple increased signal intensities over the left frontal, parietal and temporal areas. There were no ragged-red fibers, but paracrystalline inclusion bodies were shown in the muscle biopsies under electron microscopic examination. A deficiency of NADH-CoQ reductase was also found in biochemical studies of the muscles. The family survey revealed no abnormal findings except for headache and episodic vomiting in her mother. The molecular analysis of mtDNA disclosed a mutation from A to G at the nucleotide pair 3243 of the mitochondrial transfer RNA^Leu gene in the blood, hair follicles and/or muscle of the maternal relatives. A characteristic finding of the MELAS family is variation of percentage of mutated mtDNA in various tissues and individuals. However, a higher proportion of mutated mtDNA was noted in the proband than that in the asymptomatic or oligosymptomatic family members. From the data, the variable clinical phenotypes in this MELAS family can be explained at least partly, by the different proportions of mutant mtDNA in the target tissues of the profound and maternal relatives.     

Accompanying migrainous features in pediatric migraine patients with restless legs syndrome

Neurological Sciences - The present study aimed to examine the frequency of restless legs syndrome (RLS) in pediatric patients with migraine and tension-type headache (TTH) and to investigate...     

肌肉活检未见显著异常的MELAS综合征：3例病理病例分析

目的：探讨肌肉活检未见显著线粒体异常病理改变的MELAS综合征的临床、神经影像及分子病理学特点。方法：3例患者（1男,2女）,发病年龄13-18岁,1例以癫痫首发,2例以头痛呕吐首发。3例均有家族史,符合母系遗传方式。主要临床表现包括：癫痫发作(3/3例),视物下降(3/3例),发作性头痛(2/3例),听力减退 (2/3例),身材矮小（2/3例）,智能减退 (2/3例),精神异常(1/3例)。3例患者均进行肱二头肌活检。应用限制性片段长度多态方法对患者尿液mtDNA A3243G位点突变进行分析。结果：3例患者血清肌酸激酶正常,空腹血乳酸增高。肌电图检查正常。头颅MRI示T2异常高信号,枕叶3例,颞叶2例,顶叶2例,动态检查卒中样病灶呈迁徙样改变者1例。肌活检在3例患者均可见个别SDH深染的肌间小血管,未见破碎红肌纤维和COX阴性肌纤维。3例患者mtDNA基因突变分析发现均存在A3243G点突变。结论：MELAS综合征的临床异质性明显,肌无力症状可以不突出,而且肌肉活检可以没有破碎红肌纤维和COX阴性肌纤维,SDH深染的小血管可能有重要提示价值。     

MELAS: clinical features, biochemistry, and molecular genetics.

We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.     

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.     

Transient epileptic amnesia: An emerging late-onset epileptic syndrome

Transient epileptic amnesia (TEA) is a distinct neurologic condition occurring in late-middle/old age and presenting with amnesic attacks of epileptic nature and interictal memory disturbances. For many years this condition has been associated with the nonepileptic condition of transient global amnesia (TGA) and still today is poorly recognized by clinicians. Despite the clinical and laboratory findings that distinguish TEA from TGA, differential diagnosis may be difficult in the individual patient. Every effort must be employed for an early diagnosis, since antiepileptic treatment may readily control both ictal episodes and memory disturbances.     

Possible interference between migrainous and epileptic mechanisms in intercalated attacks. Case report.

The possibility that epileptic seizures and classic migraine episodes may occur in the same patient is discussed. The probable relationship between the neurophysiological mechanisms which underlie both types of attacks has not yet been agreed upon. The case of a young man who suffered from classic migraine and who presented two convulsive epileptic attacks, preceded by visual aura is described. The EEG showed an epileptogenic occipito-temporal focus which corresponded to the region of the scotoma origin. A possible connection between scotoma in migraine and epileptic discharge is discussed. It is proposed that spreading depression, as the basis of the migraine prodomata, was preceded by a moment of intense neuronal excitation which changed the epileptic intercritical activity into a critical one.     

Electro-clinical features in epileptic children with chromosome 15q duplication syndrome

ObjectiveWe aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15).MethodsClinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis.ResultsSeventy video-EEGs were analyzed (1–16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y.o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age.ConclusionWS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay.SignificanceThis study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.     

MELAS综合征和Leigh病患者的影像学观察

目的观察线粒体脑肌病伴乳酸血症和卒中样发作(MELAS)综合征和Leigh病患者的影像学特点。方法对12例MELAS综合征、7例Leigh病和1例MELAS与Leigh病叠加患者的影像学特点进行系统分析。结果 12例MELAS综合征患者脑CT及MRI示病灶多位于枕、颞、顶叶皮质及皮质下,且病灶在左侧占优势;7例leigh病患者病变部位主要在双侧基底节、丘脑及脑干。4例MELAS综合征、4例Leigh病患者、1例叠加的核磁波谱检查示病变区乳酸水平明显增高。DWI仅显示新病灶,FLAIR可观察到所有新旧病灶,较T2像敏感。MELAS可见部分病变侧MRA血管增粗增多,且病情复发时病灶有迁徙,旧病变有萎缩的特点。结论 MELAS和Leigh的影像学特点有显著差异,前者以脑叶皮质及皮质下受累为主,病变范围较大,不符合大脑动脉供血区分布。Leigh患者主要病变部位在脑干、基底节,且病灶发展变化趋势有一定的规律性。FLAIR与DWI是不可缺少的扫描像位。MRS对线粒体脑病和线粒体脑肌病的诊断有重要价值,应作为本病常规扫描序列。     

Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies

We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonus epilepsy and ragged-red fibers). Clinically, she had episodic headache, stroke-like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo-parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases Apa I and Nae I. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies.     

Hypothalamic hamartomas and ictal laughter: evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging

Detailed study of 4 patients and review of the literature allowed us to delineate further the epileptic syndrome associated with hypothalamic hamartomas, which characteristically begins in infancy with laughing seizures. Because early childhood psychomotor development is usually normal, the condition appears benign and may not even be recognized. The episodes of laughter are brief, frequent, and mechanical in nature. These features distinguish it from other forms of epileptic laughter, particularly that which occurs in temporal lobe epilepsy. Subsequently, the seizures become longer, other seizure types appear, and between the ages of 4 and 10 years, the clinical and electroencephalographic features of secondary generalized epilepsy develop. Cognitive deterioration occurs and severe behavior problems are frequent. Prognosis for seizure control and social adjustment is poor. Cortical abnormality occurs in association with the hypothalamic hamartoma. The lesions are best detected by magnetic resonance imaging but may be difficult to identify by computed tomographic scanning.     

Epidemiological and clinical aspects of cluster headache: relation with the migrainous syndrome

Neurological Sciences -     

Early infantile epileptic encephalopathy (Ohtahara syndrome) after maternal electric injury during pregnancy: etiological considerations

Early infantile epileptic encephalopathy (EIEE) is a polyetiologic age-dependent neurological disorder. We present two patients with EIEE whose mothers experienced electric injury during pregnancy. After the accident one mother noticed decreased fetal movements. Neither other prenatal factors nor intrapartal damage or postnatally examined structural, metabolic or infectious causes which might have been responsible for the EIEE in these children could be found. The question of electric accident during pregnancy should be considered when documenting the history of children with Ohtahara syndrome.     

Mutism and acute behavioral disorders revealing MELAS syndrome

Introduction

MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare genetic mitochondrial disease which can cause cerebral (cerebrovascular accident, migraine, mental deterioration..), sensorial (bilateral symmetrical deafness) and peripheral (muscular involvement, neuropathy) disorders potentially associated with diabetes, renal or cardiac disorders, or growth retardation. Eighty percent of the patients have the 3243 A > G mutation in the leucine RNA transfer gene. Clinical manifestations leading to discovery of the mutation can be extremely varied, affecting patients of different age groups.

Clinical case

We report the case of a 49-year-old man who presented acute fits of confusion followed by mutism and praxic disorders. History taking revealed recently diagnosed type 2 diabetes, axonal neuropathy, and bilateral symmetrical deafness requiring hearing aids. The initial MRI showed FLAIR sequences with bi-parietal abnormalities, no signs of recent stroke on the DW/B10000 sequences, and basal ganglia calcifications. Blood tests and morphological findings ruled out a vascular origin. Search for lactic acidosis remained constantly negative in blood samples despite positive cerebrospinal fluid samples (N × 3). The 3243 A > G mitochondrial DNA mutation was identified. The neuropsychological evaluation revealed a serious dysexecutive syndrome with a major impact on the patient's self sufficiency.

Conclusion

Neurocognitive disorders are not common in MELAS syndrome. Brain MRI results and the presence of extra-neurological signs can be helpful for diagnosis.     

CPEO and carnitine deficiency overlapping in MELAS syndrome

Mitochondrial myopathy, encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the mitochondrial encephalomyopathies that has distinct clinical features including stroke-like episodes with migraine-like headache, nausea, vomiting, encephalopathy and lactic acidosis. We report a 27-year-old woman who presented with partial seizure, stroke-like episodes including hemiparesis, hemianopia and hemihypethesia, sensorineural hearing loss, migraine-like headache, and lactic acidosis. Brain computed tomographic scan showed encephalomalacia in the right parieto-occipital area and recent hypodensity in the left temporoparieto-occipital area with cortical atrophy. Muscle biopsy revealed ragged-red fibers and paracrystaline inclusions in the mitochondria. Genetic study revealed an A to G point mutation at nucleotide position (np) 3243 of mitochondrial DNA. External ophthalmoplegia and ptosis were also found during two exaggerated episodes in this patient. Therefore, the overlapping syndrome of chronic progressive external ophthalmoplegia in the MELAS syndrome is considered in this case. Furthermore, we also found carnitine deficiency in this patient and she was responsive well to steroid therapy. Muscle biopsy also revealed excessive lipid droplets deposits. Therefore, the carnitine defiency may occur in MELAS syndrome with the A to G point mutation at np 3243. We recommend the steroid or carnitine supplement therapy be applied to the MELAS syndrome with carnitine deficiency.     

MELAS syndrome involving a mother and two children

Three familial cases of MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke) have been reported. We describe a family with four normal sons and an affected mother, son, and daughter. Although mitochondrial inheritance has been proposed, autosomal and X-linked dominant patterns are also possible. This family also illustrates the variability of expression of MELAS. The proband has the full syndrome, while the mother and daughter manifested less severe findings. All three did not develop symptoms until adulthood.     

MELAS型线粒体脑肌病的临床、影像学和肌肉病理分析

目的 探讨MELAS型线粒体脑肌病的临床表现、影像学特点和肌肉组织病理学改变,提高人们对本病的认识.方法 回顾性分析5例MELAS型线粒体脑肌病的临床表现、脑影像学改变(MRI和CT),以及骨骼肌活检的组织病理学特点.结果 MELAS型线粒体脑肌病的主要临床表现为局灶性或全身性癫NFDCC发作、听觉和视觉障碍、运动不能耐受、认知功能障碍、脑卒中样发作、血乳酸水平升高等.脑影像学检查可见病灶多位于颞、枕、顶叶皮层脑回处,脑MRI表现为长T1、长T2信号,部分患者头颅CT可见基底节钙化.骨骼肌活检5例患者肌肉组织中均可见破碎红边纤维(RRF),2例行电镜检查均可见异常线粒体聚集.结论 MELAS型线粒体脑肌病是一种以高乳酸血症和卒中样发作为特征的脑和肌肉能量代谢障碍综合征.患者临床表现复杂多样,容易造成误诊,其诊断需在临床表现和影像学特点的基础上,结合骨骼肌活检病理检查发现RRF或异常线粒体聚集,可获得临床确诊.