A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Cerebral blood flow and glucose metabolism in mitochondrial disorders.

OBJECTIVE: To investigate cerebral metabolism by 2-[18F]fluorodeoxy-d-glucose (FDG) uptake using PET and cerebrovascular reverse capacity by transcranial Doppler sonography (TCD) in different mitochondrial diseases (mitochondrial myopathy; mitochondrial encephalopathy, lactacidosis, and stroke-like episodes [MELAS]; and chronic external ophthalmoplegia). BACKGROUND: Previous studies on individual patients with mitochondriopathies revealed abnormal accumulations of mitochondria in endothelium, smooth muscle cells, and pericytes of blood vessels in different parts of the nervous system (cerebrum, cerebellum, sural nerve) and skeletal muscle. On this basis, some investigators suggested a pathogenic role of vascular involvement in the MELAS syndrome and other encephalopathies. smhd1 DESIGN/METHODS: The authors investigated neuronal metabolism and cerebrovascular involvement with PET in 5 cases and with TCD with acetazolamide stimulation in 15 cases. The patients were divided into three groups: 1) interictal MELAS (n = 4); 2) progressive external ophthalmoplegia (n = 6); and 3) pure mitochondrial myopathy and neuropathy (n = 5). The results were compared with those from matched normal control subjects. The diagnoses were based on clinical phenotype as well as histopathologic and molecular analysis. RESULTS: Cerebral glucose uptake was impaired in all patients, both with and without CNS symptoms, particularly in the occipital and temporal lobes. The vasoreactivity of the small arterioles to acetazolamide did not differ significantly between the patients and healthy control subjects or between the different groups of mitochondrial disorders. CONCLUSIONS: MELAS does not appear to be a functional disturbance of arterioles leading to an ischemic vascular event. The clinical symptoms in MELAS are not the result of a mitochondrial angiopathy but are the consequences of a mitochondrial cytopathy affecting neurons or glia. There is no correlation between the decreased glucose metabolism and the duration of the disease.

The diagnostic value of stapedius reflex and stapedius reflex exhaustion in myasthenia gravis.

Authors studies impedance, stapedius reflex thresholds and stapedius muscle exhaustion on 31 ears of 16 MG patients. Investigations were carried out using GSI 33 computer-assisted middle ear analyzator. Stapedius reflex threshold values were increased in 93% of patients. Stapedius exhaustion was observed in 71% of patients. After the administration of the reversible cholinesterase inhibitor Mestinon (60 mg pyridostigmin bromide), reflex threshold decreased and exhaustion occurred in only 50% of cases. Authors review the literature in context with the audiometric diagnostics of MG and also recommend the use of these methods in more complicated ocular and bulbar cases of MG.

Electronystagmographic analysis of optokinetic nystagmus for the evaluation of ocular symptoms in myasthenia gravis.

Ocular symptoms of 17 myasthenia gravis (MG) patients were examined by electronystagmographic registration of optokinetic nystagmus. The aim of this study was to replace the subjective methods used previously with a more reliable quantitative technique and thus assess ophthalmoplegia and diplopia, important initial symptoms in MG. Slow phase angular speed values of foveolar type optokinetic nystagmus in the horizontal plane at 10, 20 and 30 degrees/s target speed were determined. Measurements were performed before and after administration of Mestinon, a reversible cholinesterase inhibitor. Twelve healthy volunteers were examined as controls under standard conditions. Results showed significant differences between MG patients and control group. Slow-phase angular speed was significantly larger after Mestinon administration (p < 0.001). It is concluded, that the exhaustion of external ocular muscles in MG can be well characterized by the determination of the slow phase angular speed values of optokinetic nystagmus (OKN). The examination of OKN was also recommended for the evaluation of ocular symptoms in other neurological disorders.

[Phoniatric studies in myasthenia gravis patients]. / Phoniatrische Untersuchungen an Patienten mit Myasthenia gravis.

The authors have for the first time evaluated the basic parameters of the voice using computed voice analysis in patients with myasthenia gravis (MG). The aim of the study was to introduce an objective method suitable for the assessment of dysphonic symptoms, which predominate in bulbar, oculobulbar and generalized MG. Voice profile studies included the evaluation of the singing voice range, voice dynamics, maximum phonation time, and mean fundamental frequency and intensity during speech. The characteristic of the stroboscopic picture was also determined. Investigations were carried out before and after the intake of Mestinon, a reversible cholinesterase inhibitor, and healthy subjects were used as a control group. In MG, the voice range and dynamics are badly impaired, maximum phonation time is shortened, the mean fundamental frequency during speech is increased, while the intensity is decreased. Mestinon resulted in an improvement in all these parameters, however, they were still impaired in comparison to the control subjects. Most changes were found to be statistically significant. The authors emphasize the role of the otolaryngologist and objective phoniatric methods in the evaluation of MG and other myasthenia-like neurological diseases. The use of these methods for the assessment of phoniatric symptoms in neurological diseases is highly recommended.

Study of central motor functions using magnetic stimulation in Parkinson's disease.

The pathophysiological abnormalities, the contribution of activity of facilitatory and inhibitory systems to muscle rigidity and hypokinesia in Parkinson's disease are not clarified in details. Transcranial magnetic stimulation of the motor cortex may provide useful data on the functional state of motor output of the central motor structures and on the functional condition of the intracerebral motor network. The abnormalities of the central motor functions and the modifying effect of L-dopa treatment in Parkinson's disease are the objectives of our study. Patients with Parkinson's disease were examined before and after L-dopa treatment. Transcranial and cervical magnetic stimulation were performed and the latency and amplitude of the motor evoked potentials from the first dorsal interosseus muscle, the central motor conduction time and the duration of cortical inhibition were measured. The motor latency and the silent period in patients before treatment were significantly shorter than those of the age-matched healthy controls. After six months of L-dopa substitution both motor latencies and silent periods increased and approached the normal values. The observed changes are thought to be in relation to the mechanisms originating in the basal ganglia and acting through inhibitory thalamo-cortical connections at cortical level and through rubro- and reticulospinal pathways at the level of spinal inhibitory neurons. The transcranial magnetic stimulation is a suitable method to assess the efficiency of drugs in patients with Parkinson's disease.

Central core and nemaline rods in the same patient.

It is quite rare, that central cores and nemaline bodies occur in the same individual. We describe the case of a 12-year-old girl, who was born with bilateral congenital hip dislocation. Her early motor milestones were delayed. Due to proximal weakness of the lower extremities she has never been able to walk. The family history was negative. Muscle histology, histochemistry and electron microscopic studies showed a central core in nearly all muscle fibers, and nemaline rods in a few. The earlier literature and new genetical findings concerning these muscle abnormalities are also briefly summarized.

Otoacoustic emission in myasthenia gravis patients and the role of efferent activation.

We performed transient evoked otoacoustic emission (TEOAE) measurements on 29 ears of myasthenia gravis (MG) patients. The purpose of the study was to support the role of acetylcholine (ACh) in the efferent innervation of cochlear outer hair cells (OHCs). Another aim was to establish additional diagnostic tools for the early determination of MG. Initially, threshold audiometry and impedance measurements showed normal values on the ears examined. The main finding was that TEOAE values were significantly lower in MG patients than in healthy controls. Mestinon, a reversible cholinesterase inhibitor, resulted in a significant increase in mean values of TEOAEs, although these values were still lower than normal. The results suggest that in MG, acetylcholine receptor (AChR) autoantibodies inhibit the function of OHC AChRs. Thus, the TEOAE generated by the active movements of OHCs is decreased in MG. Mestinon prevents the degradation of ACh, and thus stimulates efferent function and increases TEOAE values. The results obtained in this study support the role of ACh in the efferent function of OHC, as well as the impaired function of hair cell AChRs in MG patients. Consequently, measuring TEOAEs may be useful in the early diagnosis of some forms of MG. These results reinforce the importance of collaboration between neurologists and otolaryngologists in the management of diseases with pathological neurotransmission.

Turn-amplitude analysis in neuromuscular diseases.

The first attempts in computer aided EMG analysis were performed for the automatic evaluation of interference pattern. In the routine work the turn-amplitude analysis (T/A), introduced by Stålberg and Antoni (1981), proved to be an accurate and easily performed procedure, with the advantage of being relatively independent of force. The aim of our study was to determine the diagnostic significance of T/A analysis in various neuromuscular diseases. The recordings were performed with Madaus Amplaid EMG 15, and concentric needles were used. fifty subjects had been investigated. The diagnoses were based on clinical, biochemical and histological findings. Tibialis anterior, quadriceps femoris, extensor digitorum communis and biceps brachii muscles were regularly sampled. In myogenic conditions a distinct correlation was found between the severity of muscle damage and T/A values. The more pronounced abnormalities were observed in Duchenne boys. Except the ALS in neurogenic processes correlation was found between the severity of muscle damage and T/A analysis, too. The central lesions did not have any effect on the T/A results. Examples of the possible sources of technical errors were presented and comparisons to the traditional concentric needle EMG were done.

Becker-like muscular dystrophy in sisters.

Two sisters with muscular dystrophy of Becker-like clinical features presented. Muscle weakness was most prominent in the pelvic girdle, but in the elder sister the distal muscles of the lower extremities were also affected. The progression was different in the siblings: The older sister showed a more pronounced deterioration than the younger. The family history was negative in four generations including their brother and youngest sister. Serum creatinine kinase activities increased considerably. Electromyogram and muscle biopsy specimens revealed myopathic changes characteristic of muscular dystrophy. Chromosomal analysis confirmed normal 46,XX karyotype. DNA analysis with all cDNA probes spanning the entire dystrophin gene failed to reveal any intragenic deletion or duplication on southern blot. Immunohistochemistry for dystrophin using monoclonal antibodies against the rod and C-terminal domains showed normal continuous staining at the sarcolemma of the muscle fibers in the biopsy specimens of both patients. The results practically exclude the possibility of Xp21 myopathy, and it seems reasonable to classify these patients as having autosomal recessive childhood muscular dystrophy.

[Muscle involvement in Crohn disease]. / Izomkárosodás Crohn-betegségben.

A 41-years-old man with ileitis terminalis was presented. He was operated on for chronic abdominal pain, and the histological investigation revealed the Crohn's disease. From among the extraintestinal complications the rare muscle involvement joined the inflammatory bowel disease. The leading symptoms were the progressive muscle pain and tenderness presented early before the verification of intestinal problems. His complaints referred mainly to the calf muscles. The electromyography (EMG) was normal, the serum creatinine-kinase (CK) activity has not increased. The most characteristic histological findings were the slight mononuclear cell infiltrations with large histiocytic cells in the perimysial connective tissue. Occasionally the infiltrations were more prominent resembling granuloma formations. The oxidative enzyme reactions and the electron micrographs showed mild mitochondrial changes. Neither non-steroid antiinflammatory nor steroid medication subsided the complaints.

Changes in motor and sensory nerve conduction parameters with temperature in normal and diseased nerve.

The effects of temperature on conventional motor and sensory nerve conduction parameters were studied in normals and in some pathological conditions. Surface stimulating and recording electrodes were used to examine the function of the median nerve. The motor and sensory conduction velocities, the parameters of compound muscle action and sensory nerve potentials were correlated with skin temperature. In the control subjects all nerve conduction parameters changed with temperature. These findings were similar to those published previously, but the mean slope for MCV was lower than that reported in the literature. The amplitude values widely scattered as a consequence of methodological factors, which may mask effects of temperature. Only minor differences were revealed between control subjects and patients. The effect of temperature proved to be similar in the patients and in the normal controls. Therefore, the correction factors determined in normals may be acceptable for abnormal nerves in standardising the measured values with respect to temperature. However, in pathological cases, above all in diabetes mellitus, the slightly reduced changes of conduction velocities vs. temperature may be the source of false negative results in borderline cases when using the normal correction factors. The combination of preserved temperature dependence but decreased conduction velocities may indicate that demyelination and temperature influence the conduction velocities via different mechanisms.

Scanning EMG in normal muscle and in neuromuscular disorders.

The spatial distribution of motor units in normal subjects and in patients with neurogenic and myogenic conditions was studied. The possibilities and the difficulties in quantifying the records are discussed. Normal values are presented for the brachial biceps and anterior tibial muscles. The results are compared to the previous multielectrode studies. The findings in pathological conditions compared to normals are evaluated. The scanning EMG verified the rearrangement of muscle fibres in abnormal muscles. The most striking finding was the presence of long polyphasic sections in abnormal muscles. However, this parameter did not differentiate neurogenic from myogenic cases. The length of the motor unit cross-section did not differ significantly in the abnormal muscles compared to normal. Thus, the size of motor unit territory does not seem to be a useful parameter to detect pathology. Scanning EMG gives a new dimension to exploring the motor unit characteristics not attainable by conventional methods and provides important information towards a better understanding of concentric needle EMG. Examples are shown from healthy subjects and from patients with neuromuscular diseases, both for the different parameters and special phenomena.

Decrease in the carbamylcholine-induced chemotaxis of monocytes in myasthenia gravis.

The carbamylcholine-induced chemotaxis of monocytes was decreased in patients with myasthenia gravis, whereas no change was found in the C5a-induced locomotion of these cells compared with that of the normal controls. The decrease in the chemotaxis induced by carbamylcholine correlated with the severity of clinical symptoms. The beneficial effect of thymectomy was also reflected in the improvement of chemotaxis. The method is simple, not expensive and could be used in the diagnosis of myasthenia gravis.

Inflammatory changes in facioscapulohumeral muscular dystrophy.

Fifteen patients (10 familial and 5 sporadic cases) with facioscapulohumeral dystrophy were studied with regard to the presence of inflammatory changes. Mononuclear infiltrations were not characteristic of any stage of the disease, but they may be present in differing degrees during the whole course of the process. However, their lack or presence was uniform in the affected families, suggesting that the appearance of infiltrations may be genetically determined. Parallel with the presence of cell infiltrations, the serum creatine kinase (CK) activity was moderately increased and the progress of the disease was slightly accelerated. The relation of these phenomena to polymyositis and the diagnostic difficulties are discussed.

Lipid peroxidation and superoxide dismutase activity in muscle and erythrocytes in adult muscular dystrophies and neurogenic atrophies.

Lipid peroxidation (LP) and superoxide dismutase (SOD) activity were determined in erythrocytes and skeletal muscle obtained from patients with limb-girdle and facioscapulohumeral muscular dystrophies, neurogenic atrophies and from age-matched control subjects. Neither lipid peroxidation nor SOD activity in erythrocytes of patients differed from control values. SOD activity and LP in muscle specimens were also normal in types of neurogenic atrophy. Lipid peroxidation in the muscle from patients with adult types of muscular dystrophy had a tendency to be increased. The values were widely scattered, the highest being obtained in the older patients with long duration of disease.

[Chronic Guillain-Barré syndrome (diagnostic and therapeutic possibilities)]. / Krónikus Guillain-Barré syndroma (diagnosztikus és terápiás lehetöségek).

The authors survey the clinical features and therapeutic results of their patients with chronic inflammatory polyneuropathy. There was an antecedent virus infection in the case history of 5 out of 7 patients. In one patient the chronic polyneuritis developed in association with previously verified SLE, in an other one the autopsy has proved giant lymphadenopathy. The symptoms and signs have evolved slowly in 6 patients, one patient relapsed in 4 months after the first acute attack. The initial and main symptom was the hypotonic muscle weakness of lower extremities. All of the patients mentioned paresthesias and on the lower extremities of 4 patients even hypesthesias of distal type might be revealed. The tendon reflexes were always very slow or absent. In the CSF the classical changes, excess of protein content with normal cell count were found. The electroneurography has shown increased distal latencies and reduced motor and sensory nerve conduction velocities. The steroid treatment and in 2 patients the plasmapheresis were successful, however the recovery was always incomplete and residual disabilities persisted. The electrophysiological and CSF findings did not change parallel with the relief of clinical symptoms and signs.