Descriptive epidemiology of motor neuron disease in Benghazi, Libya

A total of 23 patients with motor neuron disease (MND), encompassing 17 cases of amyotrophic lateral sclerosis, 4 of progressive muscular atrophy and 2 of progressive bulbar palsy, was diagnosed in Benghazi, north-eastern Libya, between 1980 and 1985. The male to female ratio was 2.3:1. The average incidence of MND was 0.89/100,000 population/year (0.87 when age and sex-adjusted to the Libyan population). Eighteen patients were alive on the prevalence day, September 15, 1985, which provided a prevalence rate of 3.47/100,000 population (3.42 if adjusted). Age-specific incidence rates were highest in the 50- to 59-year-old age group, 8.14/100,000/year for men and 6.10/100,000/year for women. The median age at the time of diagnosis was 51 years, and the median duration for the 5 dead MND patients after the onset of the disease was 30 months. The median survival time for all MND cases combined was 42 months.     

Descriptive epidemiology of some rare neurological diseases in Benghazi, Libya

During a 4-year study period, January 1983 to December 1986, 24 patients (18 index cases) with spinal muscular atrophy (hereditary motor neuropathy, HMN), 9 with myasthenia gravis (MG), 6 with progressive supranuclear palsy (PSP), and 5 with subacute sclerosing panencephalitis (SSPE) were diagnosed in Benghazi. The HMN group comprised 6 acute infantile, 12 chronic childhood, and 3 each with adult-onset proximal, and distal forms of the disease. The crude average annual incidence of acute infantile HMN was 0.3/100,000 total population and 1/12,500 births in Benghazi. The crude prevalence rates of chronic childhood, adult-onset proximal, and distal types of HMN were 2.3, 0.6 and 0.6/100,000, respectively. The larger family size and the high rate of consanguineous marriages contribute to the high frequency of HMN in the study area. Distal HMN constituted 12.5% of the total cases. The adjusted average incidence of MG was 4.4/million/year, 2.1 for males and 6.8 for females. The female:male incidence ratio was 3.2:1. The crude average annual incidence rates/million inhabitants for PSP asnd SSPE were 3 and 2.4, respectively. The frequency of occurrence of SSPE among the subtropical Arab community under investigation is comparable with other surveys from the Middle East and Mediterranean region.     

A clinical,epidemiological and genetic study of hereditary motor neuropathies in Benghazi,Libya

Summary A 4-year-search for spinal muscular atrophies (hereditary motor neuropathies, HMN) in Benghazi, Libya, yielded a total of 24 patients, among whom 18 were index cases. This group comprised 6 acute infantile, 12 chronic childhood, and 3 each with adult-onset proximal, and distal forms of the disorder. Distal HMN constituted 12.5% of the total cases. The crude average annual incidence of acute infantile HMN was 0.3/100,000 total population and 1/12,500 births in Benghazi. The crude prevalence rates of chronic childhood, adult-onset proximal, and distal types of HMN were 2.3, 0.6, and 0.6/100,000 respectively. The segregation ratios, 0.26 for acute infantile HMN and 0.24 for chronic childhood HMN, suggested autosomal recessive inheritance. The consanguinity rates among parents of cases and the population did not differ significantly.     

Cognitive impairment in neuromuscular disorders

Several studies have suggested the presence of central nervous system involvement manifesting as cognitive impairment in diseases traditionally confined to the peripheral nervous system. The aim of this review is to highlight the character of clinical, genetic, neurofunctional, cognitive, and psychiatric deficits in neuromuscular disorders. A high correlation between cognitive features and cerebral protein expression or function is evident in Duchenne muscular dystrophy, myotonic dystrophy (Steinert disease), and mitochondrial encephalomyopathies; direct correlation between tissue-specific protein expression and cognitive deficits is still elusive in certain neuromuscular disorders presenting with or without a cerebral abnormality, such as congenital muscular dystrophies, congenital myopathies, amyotrophic lateral sclerosis, adult polyglucosan body disease, and limb-girdle muscular dystrophies. No clear cognitive deficits have been found in spinal muscular atrophy and facioscapulohumeral dystrophy.     

Prevalence and pattern of multiple sclerosis in Benghazi, north-eastern Libya

A search for Libyan patients with multiple sclerosis (MS) was made in Benghazi, located on the southern Mediterranean coast at a latitude of 32 degrees N. Twenty-one clinically definite and probable cases were detected during the period July 1982-June 1984. On the basis of 2 probable incidental cases, the incidence for 1983 was 0.8 per 100 000 of the population at risk (10-50 years). On July 1st, 1984, the rough prevalence rate for the total population was 4 per 100 000 and the age-adjusted prevalence rate was 5.9 per 100 000. This study suggests that Benghazi falls within the medium frequency band for MS. High prevalence of brainstem involvement and cerebellar dysfunction and infrequent occurrence of the severe optic-spinal form and sphincter disturbance indicates that the present group of patients resembles Western pattern of MS as opposed to Asian MS.     

Stroke in the young: incidence and pattern in Benghazi, Libya

Out of 329 cases of stroke registered in Benghazi between November 1, 1983 and October 30, 1984, 63 patients comprising 32 males and 31 females belonged to the 15-40-year age group (stroke in the young). The annual age-specific crude incidence of stroke in the young was 39.3 and 40.3 per 100,000 for men and women, respectively. The age-adjusted incidence rate for both sexes for the age-specific (15-40 years) population was 47 per 100,000. The sex-dependent difference in the incidence was not statistically significant. These results emphasize that the high incidence of stroke in the young in Benghazi is not a reflection of the age distribution of the population. Hypertension, diabetes mellitus, heart disease and hypercholesterolemia were important components of high stroke profile in the young. One or more risk factors were identified in 78% of total young stroke victims and in all the patients under the age of 30. Eight young stroke subjects died during the study period.     

Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I

OBJECTIVES: To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self-reported questionnaires in a large sample of patients with adult-onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory neuropathy type I (HMSN-I), and to assess whether psychiatric comorbidity is related to fatigue severity and/or muscle strength. METHODS: In a cohort of 217 patients with a neuromuscular disorder (79 DM, 65 FSHD and 73 HMSN-I patients) overall psychiatric comorbidity was studied cross-sectionally with the structured clinical interview for DSM-IV axis I disorders. Self-reported psychopathology, fatigue severity and muscle strength were assessed with the Beck Depression Inventory, Symptom Checklist-90, General Health Questionnaire-12, Checklist Individual Strength and muscle strength [Medical Research Council (MRC)-scale]. RESULTS: In all three neuromuscular disorders (DM, FSHD and HMSN), 10-12% of the patients met DSM IV clinical criteria for current psychiatric disorders. Lifetime psychiatric disorders were found in 32% of patients in all three patient groups. The most common psychiatric disorders were depression and phobias. A comparison of patients with and without current psychiatric disorder showed that fatigue severity and muscle strength (MRC) were not related to psychiatric comorbidity. CONCLUSION: Psychiatric disorders appear equally in patients with DM, FSHD and HMSN-I and are not related to fatigue or muscle strength in these patients.     

The epidemiology of eating disorders in Fyn County, Denmark, 1977-1986.

The occurrence of anorexia nervosa and bulimia in Fyn County, Denmark is described. Incidence was estimated from national and local registers. The DSM-III-R criteria of one or both eating disorders were met by 104 patients. The incidence of anorexia nervosa for females 10 to 24 years of age was 11.0 per 100,000 per year. In the same population, the incidence of bulimia was 5.5 per 100,000 per year. Prevalence was estimated from questionnaires to and interviews with general practitioners. There were 193 cases; the prevalence of anorexia nervosa was estimated at 1:780 (patient years/total population years), and the prevalence of bulimia at 1:1480, in the high-risk population: females 15-19 years of age. Sixty percent of the anorexia nervosa patients, but only 30% of the bulimia patients, were admitted to hospital; this is an important difference in regard to estimation of occurrence from registers.     

Expression of myoglobin gene in skeletal muscle of patients with neuromuscular diseases

Expression of the myoglobin (Mb) gene in skeletal muscle was studied in patients with Duchenne muscular dystrophy (DMD), polymyositis (PM), or amyotrophic lateral sclerosis (ALS) by measuring Mb concentration by radioimmunoassay and Mb messenger ribonucleic acid (RNA) (MbmRNA) levels by Northern blot analysis. Mb concentrations in the muscle cells (Mb/noncollagenous protein) were decreased in patients with DMD, PM, or ALS. However, while Mb concentrations per MbmRNA content (Mb/MbmRNA) were decreased in DMD and PM patients, these values were normal in ALS patients. These results suggest that Mb synthesis is increased in muscles of DMD and PM patients, but is not sufficient to compensate for the excessive loss of Mb from the affected muscles, and that the synthesis is decreased in the muscles of ALS patients. © 1994 John Wiley & Sons, Inc.     

Prevalence of hereditary motor and sensory neuropathy in Cantabria

One hundred and forty-four patients with hereditary motor and sensory neuropathy (HMSN) were selected from within a defined area (Cantabria) in Northern Spain, from 1974 to 1984. The series comprises 49 index cases and 95 affected relatives. The prevalence ratio was 28.2 cases per 100,000. The results of the study indicate that the majority of the cases were hereditary as a dominant trait. The prevalence for the Type I HMSN cases did not differ from that of Type II cases. Previous population-surveys of these disorders are compared.     

Apoptosis is not the mechanism of cell death of muscle fibers in human muscular dystrophies and inflammatory myopathies

Muscle biopsies from patients affected by muscular dystrophies and polymyositis were processed with the method of in situ labeling of nuclear DNA fragmentation in order to assess whether apoptosis occurs in these diseases. Apoptotic nuclei were seen in the mononuclear cell infiltrates in inflammatory myopathies but not in dying muscle fibers, thus confirming the general opinion that death of muscle fibers in human diseases is not produced by a mechanism of apoptosis. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1328–1330, 1997     

Mutual interference of myotonia and muscular dystrophy in the mouse: a study on ADR-MDX double mutants

For Duchenne muscular dystrophy (DMD, dystrophin deficiency) and Thomsen/Becker myotonia (muscular chloride channel deficiency) genetically homologous mouse models are available, the dystrophin-deficient MDX mouse and the myotonic ADR mouse. Whereas the latter shows more severe symptoms than human myotonia patients, the MDX mouse, in contrast to DMD patients, is only mildly affected. We have introduced, by appropriate breeding, the defect leading to myotonia (Clc1 null mutation, adr allele) into MDX mice, thus creating ADR-MDX double mutants. The expectation was that, due to mechanical stress during myotonic cramps, the ADR status should symptomatically aggravate the muscle fibre necrosis caused by the dystrophin deficiency. The overall symptoms of the double mutants were dominated by myotonia. Weight reduction and premature death rate were higher in ADR-MDX than in ADR mice. Sarcolemmal ruptures as indicated by influx into muscle fibres of serum globulins and injected Evans blue were found with great inter-individual variation in MDX and in ADR-MDX muscles. Affected fibres were found mainly in large groups in MDX but single or in small clusters in ADR-MDX leg muscles. The symptoms of myotonia (aftercontractions, shift towards oxidative fibres) were less pronounced in ADR-MDX than in ADR muscles. Conversely, numbers of damaged fibres as well as the percentage of central nuclei (an indicator of fibre regeneration) were significantly lower in ADR-MDX than in MDX skeletal muscles. Thus it appears that, at the level of the muscle fibre, myotonia and muscular dystrophy attenuate each other.     

Changes in multiple sclerosis epidemiology in Finland over five decades

Finland is a high-risk region for multiple sclerosis (MS) with several epidemiological studies on the subject published since 1964, but these have not been comprehensively scrutinized. The objective of this study was to review previous studies of Finnish MS epidemiology, introduce new data on MS prevalence in western parts of Finland and do further analyses on data from previous studies. We performed a systematic search on articles regarding MS epidemiology in Finland in PubMed database, and all relevant articles were included in this review. MS prevalences in the western hospital districts of Vaasa, South Ostrobothnia and Pirkanmaa were calculated in 1980-2007 by using previously unpublished data obtained from a retrospective search from hospital administrative registries. To enhance comparability of the epidemiological figures, we calculated age-standardized prevalence of MS from the new data from western hospital districts and previous data from North Ostrobothnia, Southwest Finland and North Karelia. Marked regional differences in MS epidemiology were confirmed with concentration of the disease in the western and south-western parts of the country. The highest regional age-standardized MS prevalence of 288/100 000 was reported in South Ostrobothnia in 2007. A clear and stable increase in MS prevalence was observed through the decades, but the only marked increase in incidence happened in 1990s. Methodological differences hampered direct comparisons of different studies, highlighting the importance of common principles of reporting and standardizing the epidemiological figures. More comprehensive studies on MS epidemiology are still warranted to yield important information concerning the aetiology of the disease.     

Corticosteroid use in the treatment of neuromuscular disorders: empirical and evidence-based data

Corticosteroids have been used to treat neuromuscular disorders for many years. With few randomized, controlled trials, efficacy has been established primarily from empirical data. This has led to a range of treatment regimens varying in terms of initial dosing, dosing schedules, and taper rates. The goals of this review were to examine the literature for data concerning corticosteroid pharmacokinetics and for evidence-based treatment regimens in several prototypic neuromuscular disorders. The results provide a number of sound principles for corticosteroid use, but also indicate that corticosteroid regimens and patient management are largely based on empirical clinical experiences.     

Genetic epidemiology of myotonic dystrophy in Istria, Croatia

Objectives – We evaluated epidemiology of myotonic dystrophy in Istria, Croatia including direct mutation analysis as an additional, specific diagnostic criterion. Material and methods – Patients were ascertained in the period 1980–1994 from multiple sources under established clinical criteria with a special reference to congenital and minimal forms of the disease. Additionally, patients and their relatives were evaluated by direct mutation analysis. The prevalence, corrected for underascertainment, was estimated on July 1, 1989. Results – A total of 33 DM patients from nine families were ascertained. In all families the diagnosis was confirmed by mutation analysis of the DM gene. After correction for underascertainment the prevalence of 18.1/100,000 was calculated. Conclusion – One of the highest prevalence estimates of DM in the populations without evidence of founder effect or genetic isolation was found. Our results imply the importance of ascertainment of patients with all forms of DM and utilization of specific diagnostic tests for estimation of genetic epidemiology in DM.     

Motor neuron disease in the Province of Turin, Italy, 1971-1980

The incidence and prevalence of motor neuron disease (MND) in the Province of Turin, North-West Italy, were investigated for the period 1971-1980. The crude incidence rate of MND was 0.67/100,000/year. The annual incidence rate, age and sex adjusted to the Italian population in 1971 was 0.69 cases per 100,000 inhabitants, 0.94 for men and 0.45 for women, with a male to female incidence ratio of 2.09:1. The prevalence of MND was 2.62/100,000, 3.57 for males and 1.71 for females. The mean age at the time of diagnosis was 55.6 years. Annual incidence rates increased with advancing age. Amyotrophic lateral sclerosis was found to be 4 times more frequent than progressive muscular atrophy (0.53/100,000/year v. 0.14/100,000/year). The distribution of MND was uneven in the Province suggesting a proportional relationship to the distribution of population density. Possible explanations of this finding are discussed.     

Distinguishing neuromuscular disorders based on the passive electrical material properties of muscle

Introduction: The passive electrical properties of muscle, including conductivity and permittivity and their directional dependence, may be altered in neuromuscular disease; however, the character of these alterations is unknown. Methods: Fifteen wild‐type mice, 13 amyotrophic lateral sclerosis mice, 9 muscular dystrophy (mdx) mice, and 15 mice with induced disuse atrophy were euthanized, and the gastrocnemius was excised. A 50‐kHz current was applied immediately to the ex vivo muscle, and its material properties were calculated. Results: The disease groups showed distinct material property values [F(12, 119) = 14.6, P < 0.001] according to MANOVA. Post‐hoc tests confirmed that differences existed between all 4 groups. They were most pronounced in the mdx mice, which had markedly increased conductivity. Direction‐dependent properties of current flow also were significantly different among the groups (P < 0.001). Conclusions: These data confirm that the inherent passive electrical properties of muscle differ by disease type. We anticipate that similar data could eventually be obtained via surface measurements, providing an innovative approach to muscle disease diagnosis. Muscle Nerve 51 : 49–55, 2015     

Encephalomyelitis,brain tumors,neuromuscular diseases and miscellaneous disorders

Japanese neuropathologists have accomplished and contributed to a considerable number of achievements, and some of these are cited in other articles in this issue. Several of these achievements as well as other miscellaneous discoveries are briefly summarized in the present paper. Specifically these relate to rabies postvaccinal encephalomyelitis, experimental allergic encephalomyelitis, brain tumor research, neuromuscular disorders, schizophrenia, viral infections, glial inclusion body in multiple system atrophy, and the neurobiology of glia.     

Seeking a better landscape for therapy development in neuromuscular disorders

Although the neuromuscular field has seen accelerated approval of a drug for Duchenne muscular dystrophy (DMD) and full approval of one for spinal muscular atrophy, these experiences have shown that objective data and an adequate level of effect are essential for drug approval and reimbursement. The appropriateness and validity of biomarkers and clinically meaningful endpoints and an understanding of disease progression rates all played essential roles in the levels of evidence for these drugs. Such tools are best developed through integration of clinical data. The siloing of clinical data for rare neuromuscular diseases represents a considerable barrier to achieving better care and novel therapies for patients living with neuromuscular diseases. We discuss a data‐sharing model implemented for DMD and urge cultural changes in the ways natural history and clinical trial data are collected and shared across all neuromuscular diseases in order to benefit the primary stakeholder, the patient. Muscle Nerve 57 : 16–19, 2018