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ObjectivesTo assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM).MethodsTwelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test–retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation.ResultsAt 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS.ConclusionsPMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.

IntroductionBoth prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown.MethodsBased on the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”, we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype.ResultsAtaxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam.ConclusionMovement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.

ObjectiveA multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool.Design/methods17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis.ResultsIn a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW.ConclusionsLOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”. We distinguished patients with ocular myopathy as part of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with isolated ocular myopathy from PEO-plus when PEO was associated with additional features of multisystemic involvement. Ocular myopathy was the most common feature in our cohort of mitochondrial patients. Among the 722 patients with a definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%) and was positively associated with mtDNA single deletions and POLG mutations. Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy, n  = 131) was linked to the m.3243A>G mutation, whereas the other “PEO” patients ( n  = 268) were associated with mtDNA single deletion and Twinkle mutations. Increased lactate was associated with central neurological involvement. We then defined, among the PEO group, as “pure PEO” the patients with isolated ocular myopathy and “PEO-plus” those with ocular myopathy and other features of neuromuscular and multisystem involvement, excluding central nervous system. The male proportion was significantly lower in pure PEO than PEO-plus. This study reinforces the need for research on the role of gender in mitochondrial diseases. The phenotype definitions here revisited may contribute to a more homogeneous patient categorization, useful in future studies and clinical trials.

Muscle pain may be part of many neuromuscular disorders including myopathies, peripheral neuropathies and lower motor neuron diseases. Although it has been reported also in mitochondrial diseases (MD), no extensive studies in this group of diseases have been performed so far. We reviewed clinical data from 1398 patients affected with mitochondrial diseases listed in the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”, to assess muscle pain and its features. Muscle pain was present in 164 patients (11.7%). It was commonly observed in subjects with chronic progressive external ophthalmoplegia (cPEO) and with primary myopathy without cPEO, but also—although less frequently—in multisystem phenotypes such as MELAS, MERFF, Kearns Sayre syndrome, NARP, MNGIE and Leigh syndrome. Patients mainly complain of diffuse exercise-related muscle pain, but focal/multifocal and at rest myalgia were often also reported. Muscle pain was more commonly detected in patients with mitochondrial DNA mutations (67.8%) than with nuclear DNA changes (32.2%). Only 34% of the patients showed a good response to drug therapy. Interestingly, patients with nuclear DNA mutations tend to have a better therapeutic response than patients with mtDNA mutations. Muscle pain is present in a significant number of patients with MD, being one of the most common symptoms. Although patients with a myopathic phenotype are more prone to develop muscle pain, this is also observed in patients with a multi system involvement, representing an important and disabling symptom having poor response to current therapy.

To present the case of an anterior hip dislocation in an intercollegiate football player. Early detection and prompt treatment are essential for minimizing complications and acquiring the desired result. While attempting to deflect a pass, a 22-year-old male intercollegiate football player landed directly on a flexed right knee while the opposing player landed on his chest and forced him into trunk/hip extension. Past medical history was unremarkable for any previous hip/pelvis injuries. An immediate on-field evaluation was conducted and the athlete presented with an externally rotated and abducted lower extremity while lying in the supine position. There was no obvious leg length discrepancy or pelvic deformity. Upon direct impact with the ground, the athlete described feeling a \"pop\" in his hip. tie was unable to flex his right hip and unwilling to attempt to move from the supine position. Differential Diagnosis: proximal femur fracture, acetabular fracture, pelvis fracture, anterior superior iliac spine avulsion (sartorius or rectus femoris origin), slipped capital femoral epiphysis, iliac spine contusion (hip pointer), pubic diastasis, hip sprain/strain. Treatment: The athlete was stabilized on a long spine board and transported to a nearby medical facility. Radiographic evaluation of the pelvis and hip revealed a dislocation about the right hip without an associated femoral fracture. Additionally, the lateral view confirmed that the dislocation appeared anterior. There was no proximal femoral fracture or acetabular fracture. The athlete was sedated and a closed reduction was successfully achieved by traction, followed by extension and internally rotation. Post-reduction x-rays revealed no dislocation nor femoral and/or acetabular fracture. No other lesions were detected. The athlete was hospitalized and observed for 24 hours. For the next four weeks, the athlete remained nonweight bearing on crutches and began gentle range of motion exercises. At the fifth week, partial weight bearing with one crutch and mild isometric exercises were initiated. Periodic radiographic evaluation revealed no articular changes about the femoral head. Uniqueness: Approximately 3% of all joint dislocations occur to the hip. Specifically, 8-10% of hip dislocations occur anteriorly. Most hip dislocations occur following a high-energy event, such as a motor vehicle accident. Traumatic dislocations of the hip represent a major injury in sport and are extremely rare, particularly anterior luxations. A thorough understanding of the clinical signs and symptoms are essential if this injury is to be recognized and managed appropriately. Early recognition and treatment of the traumatic hip dislocation substantially reduces the likelihood of complications arising from this injury. With prolonged time and multiple attempts for reduction, there is an increased risk for neurovascular compromise and degenerative changes of the femoral head. Specifically, such delays may alter the vascular integrity and progressively lead to osteonecrosis of the femoral head.

To present the case of exertional rhabdomyolysis in an intercollegiate football player. A 19-year-old male intercollegiate football player was participating in pre-season camp when he began to develop severe muscular aches. Chief complaint was achiness in the abdominal and lower extremity muscles and associated joint aches. During early morning conditioning drills (50-yard sprints), the athlete first described muscular pain during any running and/or exertional activities. The athlete denied any nausea/vomiting or change in bowel habits. Patient reported to the athletic training staff with fevers up to 104 degree F with some intermittent headaches and associated muscle aches, as well as a thready pulse. Past medical history was unremarkable. Differential Diagnosis: dehydration, appendicitis, unspecified viral infection, lyme disease, carcinoid syndrome, acute renal failure, reperfusion, McArdle's Disease, crush syndrome, ethanol (alcoholic) myopathy. Treatment: The athlete was immediately transported to the local medical facility for further evaluation. The athlete was admitted to the hospital and treated with intravenous fluids with urinalysis and blood cultures performed. His urinalysis showed greater than 10,000 mixed BCs, slightly low white cell count (WBC) at 4.0 and slightly decreased platelets at 125. Also noted was laboratory creatine phosphokinase (CPK) values were of 1,647 and an elevated AST of 75. A chest x-ray was performed which showed the lungs to be clear, while an abdominal x-ray showed a possible left kidney stone. A subsequent CT-Scan of the abdomen and pelvis indicated a normal study with no bowel inflammation or any kidney stones noted. At 5 days s/p, he was discharged and restricted from all physical activity. Uniqueness: Additionally, he was instructed on maintaining appropriate hydration levels and discontinued any nutritional supplementation, particularly those with creatine ingredients. After nine days without symptoms the athlete was gradually returned to full, unrestricted activity. The earliest modern reports of rhabdomyolysis appear in the German literature indicating a classic triad of symptoms, muscle pain, weakness and brown urine, known as Meyer Betz disease. In 1941, Bywaters and Beall identified the first causative association between rhabdomyolysis and acute renal failure during World War II. Rhabdomyolysis is a clinical and biochemical syndrome resulting from skeletal muscle injury with release of muscle contents, specifically myoglobin into the plasma. It may or may not result in visible myoglobinuria, i.e., red or brown urine. While the precise pathogenesis of rhabdomyolysis is not clearly understood, rhabdomyolysis has been implicated as a major cause of acute renal failure. Rhabdomyolysis results from direct muscle injury or an altered metabolic relationship between energy production and energy consumption in muscle. Rhabdomyolysis is a potentially lethal syndrome with a broad spectrum of clinical and biochemical findings. The clinical symptoms and signs vary widely from myalgia to severe muscle weakness with involvement of other organ symptoms. Early and aggressive volume replacement is essential in order to reduce further systemic complications and depends on the severity of myoglobinuria.

Background: Gastric juice may give important clinico-pathological information, but measurements in this medium are difficult. In this study we present and validate an innovative device (Mt 21-42) performing gastric juice analyses during endoscopy and proposed for the endoscopic diagnosis of Helicobacter pylori infection and hypo/achlorhydria. Methods: Analyses on both aqueous solutions (80 pH buffer + 120 ammonium chloride samples) and human gastric juice were carried out to assess the measuring performance of Mt 21-42 on the ideal and real matrix, respectively. Matrix spike and manipulation tests were also performed to investigate the matrix effect of gastric juice and to evaluate the consequences of its manipulation on the measurements. Furthermore, preliminary clinical tests were performed to evaluate the clinical potentiality of the device. Results:Mt 21-42 showed a good measuring performance on ideal matrix (coefficient variation: pH = 1.3%, ammonium = 2.1%) and real matrix (coefficient variation: pH = 1.2%, ammonium = 1.9%). Analyses on gastric juice excluded a substantial matrix effect (percent recovery =96.5–98.7%) but demonstrated a significant influence of manipulation procedures (p < 0.05). Conclusions: Human gastric juice does not have a substantial matrix effect for pH and ammonium determination, but its manipulation may affect the measurement of these components. Mt 21-42 represents a precise instrument for the measurement of gastric juice and a potential precious tool for the endoscopic detection of H. pylori infection and hypo/achlorhydric conditions.