Involvement of pelvic girdle and proximal leg muscles in early oculopharyngeal muscular dystrophy.

Although limb girdle weakness is not part of the major diagnostic criteria of oculopharyngeal muscular dystrophy (OPMD), it has frequently been observed in the Dutch and other OPMD cohorts. In the Dutch cohort, this might be related to the relatively old age or the severity of the genetic defect. This patient-control study (14 OPMD patients and 12 controls) investigated the involvement of limb girdle muscles with a multidimensional approach in early OPMD. We assessed functional abilities, disease impact, physical activity, muscle strength, histopathology and fatty infiltration using questionnaires, actometer, functional tests, manual and quantitative muscle testing, muscle biopsy and muscle MRI. The study showed that involvement of pelvic girdle and proximal leg can be a relatively early feature of OPMD, resulting in impaired daily life activities. The fat fraction of the hip adductors and hamstrings was significantly higher in OPMD patients than in controls. Future studies should include assessment of hip flexors, hip adductors and hamstrings (muscle strength measurements and MRI), functional tests and questionnaires. These findings are important in future diagnostics, management and for the design of outcome measures in trials.

Intranuclear Aggregates Precede Clinical Onset in Oculopharyngeal Muscular Dystrophy.

BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilateral ptosis and dysphagia and subsequent limb girdle weakness. The role of the typical intranuclear inclusion in the pathophysiology is unresolved. OBJECTIVE: The aim of this study was to describe the clinical and histopathological features of oculopharyngeal muscular dystrophy (OPMD). We examined this in a Dutch cohort including presymptomatic Ala-expanded-PABPN1 carriers and late symptomatic patients. METHODS: We performed a prospective, observational study in OPMD patients and adult children of genetically confirmed OPMD patients. The study includes a structured history, a detailed neurological examination, muscle histology and biochemical analysis. Forty patients and 18 adult children participated in this study, among whom were six presymptomatic mutation carriers. One patient died during the study and had given permission to autopsy. RESULTS: In addition to the characteristic OPMD symptoms including ptosis and dysphagia, other symptoms such as limb girdle and axial weakness, and external ophthalmoplegia were frequently observed. Intranuclear aggregates were observed in the biopsies of presymptomatic carriers. Biochemical analysis of the biopsies of the presymptomatic carriers showed no mitochondrial dysfunction. The autopsy showed that muscle weakness correlated with histopathological findings in five different muscles in an individual patient. CONCLUSIONS: The main findings of this nationwide study are the presence of intranuclear aggregates before clinical onset and the absence of mitochondrial changes in Ala-expanded-PABPN1 carriers. This indicates that the expression of Ala-expanded-PABPN1 causes the formation of nuclear aggregates before the onset of muscle weakness. Normal results of biochemical analysis in presymptomatic carriers suggest that possible mitochondrial dysfunction occurs later. Furthermore we confirmed that limb girdle weakness occurs frequently in Dutch OPMD patients. This study thus expands the OPMD research towards characterization of presymptomatic carriers.

Ptosis aggravates dysphagia in oculopharyngeal muscular dystrophy.

BACKGROUND: Ptosis and dysphagia are important features in oculopharyngeal muscular dystrophy (OPMD). OBJECTIVE: Retroflexion of the head is a well known compensatory mechanism for ptosis, but generally retroflexion has a negative effect on swallowing. We hypothesised that severity of ptosis is related to degree of retroflexion and that this compensation is responsible for deteriorating dysphagia. METHODS: Nine OPMD patients were examined in the conditions "head position adapted to ptosis" and "head position slightly flexed". Ptosis was quantified by photogrammetry and retroflexion of the head by digital photographs. The severity of dysphagia was measured using visual analogue scales (VAS) and by calculating swallowing volumes and oropharyngeal swallow efficiency (OPSE) based on videofluoroscopy. RESULTS: Statistical analyses show a significant relationship between ptosis and degree of retroflexion. The degree of retroflexion of the head correlated significantly with VAS scores and with the maximum swallowing volume. The slightly flexed head position significantly improved VAS scores as well as swallowing volumes and OPSE. CONCLUSION: In OPMD patients, ptosis significantly correlates with retroflexion of the head, which has a negative effect on swallowing. Subjective and objective reduction of swallowing problems was found when patients were instructed to eat and drink with a slightly flexed head position.

Autosomal recessive oculopharyngodistal myopathy: a distinct phenotypical, histological, and genetic entity.

We present a 25 year follow up of two siblings with autosomal recessive (AR) oculopharyngodistal myopathy. Remarkable in these patients, in comparison with patients with oculopharyngeal muscular dystrophy (OPMD), are the earlier age of onset, severe facial weakness, external ophthalmoplegia early in the course of the disease, and distal weakness in the limbs. Histological features included basophilic-rimmed vacuoles, but the typical OPMD intranuclear filaments were absent. These clinical and histological characteristics are comparable with those of two Japanese patients with AR oculopharyngodistal myopathy. This myopathy has usually been described as an autosomal dominant (AD) muscle disorder. It shares some clinical and histological characteristics with OPMD, but most patients with AD oculopharyngodistal myopathy are genetically different. Here we exclude an expansion of the GCG repeat or any other mutation in the coding region of the PABPN1 gene (responsible for OPMD) in patients with AR oculopharyngodistal myopathy. From this we conclude that AR oculopharyngodistal myopathy is a distinct phenotypical, histological, and genetic entity.

Brain tumour as a rare cause of cardiac syncope.

We report on a patient with a bradycardia followed by an asystole as expression of a complex partial seizure arising from a cerebral neoplasm in the medial part of the left temporal lobe. Previously published papers have shown that cardiac asystole and bradycardia as manifestation of epilepsy originate from the temporal lobe. Although seizures are a common presenting symptom of a cerebral neoplasm, bradycardia and cardiac asystole of epileptic origin as first sign of a cerebral neoplasm is only sporadically documented in literature. Many different regions of the central nervous system are involved in the cardiovascular control. When a patient with a collapse is admitted to the emergency room it often is difficult to differentiate between cardiological and neurological aetiologies. However, it is important to identify the origin of a collapse in order to start the right treatment and give correct information to the patient and his family. Therefore, in patients with a non-typical cardiac syncope, a primary neurological cause should be considered.