Turkish version of the Motor Function Measure Scale (MFM-32) forneuromuscular diseases: a cross-cultural adaptation, reliability, and validity study

Background/aim: The Motor Function Measure (MFM-32) is a classification system for ambulant and nonambulant patients with neuromuscular diseases (NMDs). We aimed to translate it into Turkish, culturally adapt it, and test its reliability and validity for Turkish patients with NMDs.Materials and methods: The translation of the 32 items assessing three functional areas: standing position and transfers (D1: 13), axial/proximal (D2: 12), and distal (D3: 7) motor functions was performed according to the established guidelines for cross-cultural adaptation. Totally 51 patients (12.56 ± 8.84 years; F/M 12/39) were tested. Vignos and Brooke scores for the lower and upper extremities, respectively, were used for the validity of the MFM-32-TR items, which were rated on a 4-point Likert scale. Results: The agreement coefficients for interrater reliability were excellent (0.72-0.93) for 10 items, good (0.58-0.77) for 16 items, and moderate (0.42-0.56) for 6 items of the MFM-32-TR. The intertester reliability varied from good to excellent and the intraclass correlation coefficient was 0.76-0.93. The MFM-32-TR positively correlated with Vignos and Brooke scores with coefficients 0.47 to 0.75, indicating concurrent validity.Conclusion: The MFM-32-TR is a reliable and valid outcome measure for the assessment of motor function of people with NMDs in our sociocultural context.

The prevalence of neuromuscular disease in the paediatric population in Yorkshire, UK; variation by ethnicity and deprivation status.

AIM: Previous studies suggest a higher prevalence of neurological disease within certain ethnic communities, but have not specifically considered neuromuscular diseases (NMDs). The aim of this study was to calculate the prevalence and relationship of NMDs to ethnicity and deprivation status. METHOD: We undertook a retrospective case-note review of those younger than 16 years with a confirmed diagnosis of NMD in a single centre in Yorkshire in 2010. RESULTS: Two-hundred and sixty-one cases were included. The population (0-16y) in Yorkshire was 707 961. The overall prevalence was 36.9 per 100 000 (95% confidence interval [CI] 34.6-39.1). Dystrophin-related muscle disease was the most common condition, with a prevalence of 16.9 per 100 000 males (95% CI 14.7-19.1). There was a significant difference between ethnic groups, with a total NMD prevalence of 91.2 per 100 000 (95% CI 81.6-100.7) in the South Asian ethnic group compared with 28.7 per 100 000 (95% CI 26.4-30.9) in the White group. Prevalence of non-dystrophin-related NMDs was four times higher in South Asian than in White children. There was a linear relation between increased prevalence and increased deprivation. INTERPRETATION: This study confirms higher levels of NMD, particularly recessively inherited NMDs within the South Asian population, as well as a link with higher deprivation. This has implications for service provision and resource allocation.

Functional cellular analyses reveal energy metabolism defect and mitochondrial DNA depletion in a case of mitochondrial aconitase deficiency.

Defects in the tricarboxylic acid cycle (TCA) are associated with a spectrum of neurological phenotypes that are often difficult to diagnose and manage. Whole-exome sequencing (WES) led to a rapid expansion of diagnostic capabilities in such disorders and facilitated a better understanding of disease pathogenesis, although functional characterization remains a bottleneck to the interpretation of potential pathological variants. We report a 2-year-old boy of Afro-Caribbean ancestry, who presented with neuromuscular symptoms without significant abnormalities on routine diagnostic evaluation. WES revealed compound heterozygous missense variants of uncertain significance in mitochondrial aconitase (ACO2), which encodes the TCA enzyme ACO2. Pathogenic variants in ACO2 have been described in a handful of families as the cause of infantile cerebellar-retinal degeneration syndrome. Using biochemical and cellular assays in patient fibroblasts, we found that ACO2 expression was quantitatively normal, but ACO2 enzyme activity was <20% of that observed in control cells. We also observed a deficiency in cellular respiration and, for the first time, demonstrate evidence of mitochondrial DNA depletion and altered expression of some TCA components and electron transport chain subunits. The observed cellular defects were completely restored with ACO2 gene rescue. Our findings demonstrate the pathogenicity of two VUS in ACO2, provide novel mechanistic insights to TCA disturbances in ACO2 deficiency, and implicate mitochondrial DNA depletion in the pathogenesis of this recently described disorder.

Clinical impact of persistent hyperCKemia in a Norwegian general population: a case-control study.

In this case-control study we assessed the clinical impact of persistent hyperCKemia in a Norwegian general population. HyperCKemia was defined according to the NORIP- references (women 35-210 U/L, men <50 years 50-400 U/L, and men ≥50 years 40-280 U/L). We compared the frequency of muscular symptoms and function, neuromuscular diseases and risk factors between 120 cases with persistent hyperCKemia and 130 age- and sex-matched controls with normal CK values, all recruited from the single-centre, population-based prospective Tromsø Study. The participants underwent a standardized interview assessing muscle symptoms, physical activity, use of statins and presence of other CK risk factors, prior to clinical neurological and neurophysiological examination. Knee extensor muscle strength (Cybex NORM dynamometer) and dominant hand grip strength (Martin Vigorimeter) was assessed. A total of 85 cases (71%) reported either muscle pain, muscle stiffness or cramps, compared to 70 controls (54%) (p=0.017) There were no differences in muscle strength between the groups. In men, weight, Body Mass Index and muscle symptoms were significantly higher in the group with persistent hyperCKemia. In women, no differences between the groups were detected. Use of statins was similar in cases and controls. We diagnosed 3 women with previously unknown myopathy, all in the group with persistent hyperCKemia. This study support that CK may be used as a marker of muscular symptoms in the general population.

Neuromuscular disorders in the Gypsy ethnic group. A short review.

The Roma (Gypsies) are a transnational minority with an estimated population of 10 to 14 million, 8 of which reside in Europe, scattered between the Balkans and Western countries. Similar to other genetically isolated founder populations, the Roma harbour a number of unique or rare autosomal recessive disorders, caused by "private" founder mutations. These genetically homogeneous populations are a unique resource for research into disease phenotypes, genotype/phenotype correlations and possible factors modifying clinical severity. Regarding neuromuscular diseases, the following have been identified: limb girdle muscular dystrophy type 2C also called gamma-sarcoglycanopathy, congenital myasthenic syndrome type 1a, spinal muscular atrophy, and three novel hereditary sensorimotor neuropathies, namely -Lom, -Russe and the congenital cataracts facial dysmorphism neuropathy syndrome. In 1996, a novel demyelinating neuropathy in the Roma was described and the gene was mapped in 8q24. Almost simultaneously, a founder mutation in the gamma-sarcoglycan gene in a group of 24 Romani patients from France, Spain and Italy was discovered by a different group of researchers. The cooperation between these two groups and people from several European countries was fruitful, and in 2001 the 91st Workshop of the European Neuromuscular Center was organized to discuss the above-mentioned diseases in the Roma. Full papers on each of the topics were subsequently published in the 20th Anniversary volume of Acta Myologica, in December 2001. Here, we present a short review of neuromuscular disorders in Gypsies and we discuss the perspectives and future for further studying and research.

[Neuromyelopathy in the population of Noir-marron of Saint-Laurent du Maroni in French Guiana]. / Neuromyélopathies dans la population de Noirs marrons de Saint-Laurent du Maroni en Guyane française.

The neurological observations have been reported at André Bouron Hospital of Saint-Laurent du Maroni and at General Hospital of Cayenne during a period of 5 years. All patients belonged to the "Noir Marron" ethnic group and lived in the area of Saint-Laurent. There were six women and four men, aged 15-35 years. Neurological symptoms were isolated or associated to other organ failure. Neurological manifestations included retrobulbar optic neuropathy, spastic paraparesis, sensitive ataxia and cerebellar ataxia, psychiatric symptoms were observed. Other organs affected were cardiovascular, digestive, cutaneous or endocrinologic (thyroid). Diet consist mainly in cassava. Thiamin deficiency has been observed several times. Improvement of neurological deficits following thiamin administration points towards Thiamin as an etiological factor. Ethnological specificity of Saint-Laurent area may explain that such neurological manifestation have not been observed in the rest of the department.

Single fiber EMG in a congenital myasthenic syndrome associated with facial malformations.

Six patients with a newly described genetic syndrome in Iraqi and Iranian Jews of congenital myasthenia associated with facial malformations were studied with voluntary and stimulation single fiber EMG (SFEMG). Voluntary SFEMG revealed abnormal jitter in all patients in both extensor digitorum communis (EDC) and orbicularis oculi (OOC) muscles, though much smaller in the clinically unaffected EDC. SFEMG study of OOC muscle by axonal stimulation at rates from 1 to 48 Hz showed the most increased jitter at the highest stimulation frequencies in the majority of end-plates, one-third of which showed maximal jitter at intermediate rates. These results may suggest a postsynaptic abnormality as the underlying cause for the neuromuscular transmission defect, and demonstrate the usefulness of SFEMG in the diagnosis of congenital myasthenia.

Congenital myasthenia associated with facial malformations in Iraqi and Iranian Jews. A new genetic syndrome.

Fourteen Jewish patients from 10 families of either Iraqi or Iranian origin with congenital myasthenia had associated facial malformations which included an elongated face, mandibular prognathism with class III malocclusion and a high-arched palate. Other common features were muscle weakness restricted predominantly to ptosis, weakness of facial and masticatory muscles, and fatigable speech; mild and nonprogressive course; response to cholinesterase inhibitors; absence of antibodies to acetylcholine receptor; decremental response on repetitive stimulation at 3 Hz but no repetitive compound muscle action potential in response to a single nerve stimulus. This newly recognized form of congenital myasthenia with distinctive ethnic clustering and associated facial malformations is transmitted as an autosomal recessive disorder. The facial abnormalities may be secondary to the neuromuscular defect or may be primary and unrelated. Further studies are needed to elucidate the defect in neuromuscular transmission responsible for the pathogenesis of this syndrome.

Rising mortality from motoneuron disease in the USA, 1962-84.

From 1962 to 1984, age-specific mortality for motoneuron disease (MND) in the United States rose in all demographic groups over the age of 40. The increase was seen in both men and women, and both whites and non-whites, and was most pronounced in the elderly (eg, 378% in white women aged 80-84 years). Men were at 50% higher risk than women, and whites had twice the risk of non-whites. These increases may reflect an improvement in case ascertainment, but they also seem to show a true rise in the incidence of MND, particularly among the elderly. Such an increase suggests an environmental aetiology.

Motor neurone disease of the western Pacific: do the foci extend to Australia?

Hyperendemic foci of motor neurone disease, and other neurodegenerative disorders, are located in the western Pacific area, in the Japanese of the Kii Peninsula of Honshu Island, the Chamorros of the Mariana Islands, the Auyu and Jakai of West New Guinea. It is suspected that there is a common aetiologic pathway from toxic metal and essential minerals in these three foci. A fourth focus of motor neurone disease occurs in an isolated tribal group living on the same Pacific longitude, at Angurugu on Groote Eylandt in the Gulf of Carpentaria, Northern Australia. This environment is also characterized by local ecological extremes, including low calcium and iron, and high manganese. The "Angurugu syndrome", described in this paper, shows dysfunction of motor neurones, including upper and lower motor, cerebellar, extrapyramidal and cranial nerves, especially oculomotor. About half the cases emerge in adult life. The others are evident in early childhood. The syndrome is viewed not as simple manganism but as manganism synergistic with accompanying mineral changes. No autopsy studies have been carried out. This paper suggests that this syndrome incurs a loss of the neurotransmitter dopamine. A case study is presented that indicates the unusual range of symptoms, including ataxia, and partial relief by L Dopa (Sinemet).

[Tropical African neuromyelopathies: 61 studied cases in the Ivory Coast]. / Neuromyélopathies tropicales africaines: 61 cas étudiés en Cote d'Ivoire.

Sixty one cases of tropical myeloneuropathies (TNM) from Abidjan, Ivory Coast, are reported. The mean age of patients was 35 years. The socioeconomic level was often very low and puerperality was a common initiating factor. Several clinical forms are noted: pure pyramidal (16 cases), pure ataxic (11 cases), sensory motor polyneuritis (8 cases), combined sclerosis of the spinal cord (1 case), ataxic polyneuritis (25 cases). In fact the extent of the pathobiological process was more severe as shown by slowings of peripheral motor nerve conduction velocities, prolonged central conduction time determined after cortical and spinal stimulations, and a severe sensory axonal impairment on nerve biopsies. These changes were observed with varying degrees in all clinical forms. As long as the etiological factors of TMN are not known (preventing from the possibility to split this disease in several entities) it is preferable to speak about one global disorder and not isolated various clinical forms (e.g. particulary: tropical spastic paraplegia). HTLV-I retrovirus seems to play a limited role in the etiology of TMN in Ivory Coast (1 positive case).

[Statistical data on hereditary nervous system diseases in Ashkhabad and Krasnovodsk Provinces, the Turkmen SSR]. / Statisticheskie dannye o nasledstvennykh zabolevaniiakh nervnoi sistemy v Ashkhabadskoi i Krasnovodskoi oblastiakh Turkmenskoi SSR.

Epidemiology and the clinical course of hereditary diseases of the nervous system were studied in the Ashkhabad and Krasnovodsk Provinces of the Turkmen SSR versus the data from other regions of the country. A detailed analysis was made of 236 cases of hereditary neural pathology. The intensity rate (21.6 X 10(-5)) of the pathology in the studied area turned to be significantly higher in the other regions considered. Such a high incidence rate was attributed to the existence of isolated communities, marriages between close relatives and a high rate of birth.