The electrophysiological profile of hereditary motor and sensory neuropathy-Lom.

OBJECTIVE: To make electrophysiological observations on a large kindred with hereditary motor and sensory neuropathy-Lom (HMSN-L) containing 27 affected individuals. CLINICAL FINDINGS: Onset was in early childhood with gait difficulty related to progressive lower limb weakness. Upper limb weakness developed later. Bulbar involvement was present in one third of the patients, and deafness appeared during the second or third decades. ELECTROPHYSIOLOGICAL FINDINGS: Electromyographic evidence of denervation was progressive, more severe distally, and greater in the legs, being total in distal lower limb muscles in most patients. Sensory action potentials were absent and motor nerve conduction was severely slowed. This included proximal upper limb (musculocutaneous and axillary), hypoglossal, and facial nerves. The severity of slowing increased during childhood. M waves, often multiple, were recorded in all affected individuals. The blink reflex showed an unusual three component response. The latencies of all three components were prolonged. CONCLUSIONS: HMSN-L is shown to be a demyelinating neuropathy involving severe and early axonal loss. The progressive slowing of nerve conduction during childhood differs from the static reduction seen in type I HMSN.

Conduction block--the diagnostic value in the early stage of Guillain-Barre syndrome.

Immune-mediated segmental demyelination is the basic pathomorphological substrate of the Guillain-Barre syndrome (GBS). The aim of the study is to determine the diagnostic value of the conduction block in the early stage of GBS, as well as its changes during of the development of the disease. Sixteen patients with GBS were examined. Electroneurography (motor nerve conduction studies) was performed at interval from the third day of the onset till the first year. Partial CB in the early stage of the disease (range 0-15 days) was registered in 81,2% of the patients. In demyelinating forms of GBS partial CB was determined in 61% of the investigated nerves. It is the most often observed in peroneal nerves, followed by tibial, ulnar and median nerves in the same order. The maximal reduction of the amplitude of the CMAP (maximal CB) was registered before the 30th day from the onset of the disease with following recovery on the sixth month and first year. Partial CB is more often observed in the early phase of GBS, when it could be the only sign of demyelination. When patients reached a clinical plateau, progressive slowing of motor nerve conduction and increasing CB were registered. Proximal CB was revealed more often than distal CB, because of the typical initial localization of the process. In the early phase of GBS, proximal CB is most often found in lower limbs (in peroneal nerve, followed by tibial nerve). In patients with axonal damage, CB was more severe than in demyelinating group. Partial CB is an important diagnostic criterion for segmental demyelination, which helps for confirming the diagnosis of early GBS, when conduction velocity and other electrodiagnostic criteria for demyelination are normal.

A-waves in patients with novel hereditary motor and sensory neuropathy Lom.

OBJECTIVES: To determine A-waves of a family with autosomal recessive form of demyelinatig hereditary motor and sensory neuropathy Lom (HMSNL). METHODS: A-waves were investigated during conventional F-wave study of family members with HMSNL which had genetic testing. RESULTS: During routine F-wave studies A-waves were observed in all tested nerves. They appeared between M-responses and F-wave. The A-waves were with low amplitude, shorter duration and constant shape and latency than F-waves. They appeared independently of F-waves. A-waves were more often recorded as multiple waves in lower and upper extremities. More than three A-waves per nerve were found mostly in ulnar and facial nerves. In 16 cases A-waves were found in the absence of F-waves. CONCLUSION: It is assumed that the A-waves could be seen as additional signs of pathology because they were not observed in unaffected members of the family and in healthy subjects.

Comparative analyse of single motor unit pattern in healthy subjects and patients with neuromuscular disorders.

OBJECTIVE: The motor unit (MU) spike trains in human muscle contractions are an object to new mathematical processing. The aim is to identify the interspike interval relations characterizing normal and changed physiological states (neuro-muscular disorders). METHODS: MU activities in healthy subjects and patients with Schwartz-Jampel syndrome, neuromiotonia and Parkinson disease were investigated. Motor unit action potentials (MUAPs) were recorded by surface multielectrode with small leading-off area without provoking a burst of activity, as usually was observed during the needle electromyography study in patients with Schwartz-Jampel syndrome and neuromiotonia. RESULTS: Different single motor unit activity in healthy subjects and patients was observed. Discharge pattern of patients was basically changed. Disturbance of different parts of the motor system leads to the changes of temporal order of interspike interval. This permit us to suppose that the pattern of repetative neuronal discharges suggests an influence at a higher level than the muscle in all investigated patients but the reason of multiple discharges with an interimpulse interval of 2 to 10 ms probably originated in the muscle membrane. CONCLUSIONS: The comparative analysis of MU patterns in healthy subjects and patients with neuro-muscular disorders can help us to disclose inapparent connections between cortical and spinal level of motor control.

The trigemino-cervical reflex in normal subjects.

There are only few reports on the trigemino-cervical reflex in humans and there is debate over the best method of reflex examination. The aim of this study was, comparing different methods, to provide a reproducible method for evaluating the trigemino-cervical reflex. The trigemino-cervical reflex was studied in 32 healthy volunteers. The stimulation was applied to the supraorbital, infraorbital or mental nerve. Recordings were performed bilaterally from the sternocleidomastoid and trapezius muscles at rest. The reflex was also examined during maximal voluntary contraction of the sternocleidomastoid muscle after supraorbital nerve stimulation. It presented as a two-component reflex if recorded from a tonically active muscle and as a one-component reflex if recorded from a relaxed muscle. The most reproducible reflex responses were obtained from the resting sternocleidomastoid muscle after stimulation of the supraorbital nerve. In conclusion, the trigemino-cervical reflex may be most easily obtained from the relaxed sternocleidomastoid muscle after supraorbital nerve stimulation.

Differential diagnosis of myasthenic syndromes.

Myasthenia-like symptoms and Eaton-Lambert myasthenic syndrome have been reported in patients with polymyositis. On the other hand, the muscular involvement in myasthenic patients is well established. Thus difficulties in the differentiation of patients with polymyositis and myasthenic syndrome and myasthenia with myopathy may arise. The aim of this investigation was to re-establish the clues for distinguishing between different types of myasthenic syndromes. One hundred and twenty five patients took part in this investigation. According to the electromyography, biopsy and serum levels of creatine kinase data, the patients were subdivided into three groups. The first group consisted of 35 patients with data for chronic polymyositis. The second group consisted of 46 patients with myasthenia. The third group consisted of 44 patients with myasthenia and myopathy. Our data confirm the more often onset of myasthenia with ptosis and of myasthenic syndromes in polymyositis-from lower limbs. The bulbar involvement is more rare, while the autonomic nervous system involvement and decreased tendon reflexes are more common in patients with Eaton-Lambert myasthenic syndrome as compared to patients with myasthenia. Bulbar involvement is more typical for myasthenia, while four limbs involvement is more common in patients with myasthenia and myopathic changes. There are no differences in the typical decrementing response between patients with polymyositis, myasthenia or myasthenia with myopathic involvement. The Eaton-Lambert myasthenic syndrome is quite different and is found only in a small part of polymyositis patients. In conclusion the differential diagnosis between myasthenic syndromes in polymyositis and myasthenia with muscular involvement is not possible only by electromyography.

Hereditary motor and sensory neuropathy--Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries.

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Differential diagnosis of amyotrophic lateral sclerosis and similar syndromes.

The aim of this investigation was to re-evaluate the electromyographic findings in patients with ALS and with localised lesions of the spinal cord and to find some clues for differentiation. Two hundred and sixteen patients took part in this investigation. They were subdivided into two groups. The first group consisted of 168 patients with data for amyotrophic lateral sclerosis. The second group consisted of 48 patients with syndrome of amyotrophic lateral sclerosis caused by cervical myelopathy. Detailed neurological and electromyographic examinations were performed to all patients. In conclusion the electromyographic findings in patients with ALS are not different than the abnormalities in muscles innervated by the affected segments in patients with localised lesions which compress the anterior portion of the spinal cord. The only clues for differentiation are the clinical signs and the distribution of electromyographic abnormalities.

Peripheral late waves in patients with hereditary motor sensory neuropathy.

Patents with different forms of hereditary motor sensory neuropathy (HMSN) were investigated. Peripheral late waves (PLWs) were recorded when determining F wave at supramaximal stimulation. We registered them most frequently in patients with demyelinating neuropathies (HMSN1--58% and HMSN3--100%) and in patients with HMSN2--24% and HMN--13%. In patients with HMSN1 and HMSN3 the peripheral late waves sometimes were more than one--two or three. They had a consistent appearance above a maximal threshold of stimulation, an invariable latency, amplitude and wave-form. Their latency times were in parallel with the M-response latency. These PLWs can be explained by collateral regeneration in case of axonal neuropathy. The ephaptic transmission might be taken in consideration when interpreting data from patients with demyelinating processes.

Comparative analysis between Duchenne and Becker types muscular dystrophy.

Duchenne and Becker types of muscular dystrophy are usually differentiated according to age of onset and rate of progression criteria which are not sufficient. The aim of this paper was to re-establish the clues for distinguishing Duchenne from Becker types of muscular dystrophy. According to the onset and progression of the disease, one hundred and eleven patients were subdivided into two groups. First group--Becker muscular dystrophy--consisted of 40 patients and second one of 71 patients with Duchenne type of muscular dystrophy. Clinical data confirm some well known differences between Duchenne and Becker muscular dystrophy concerning the age of onset, severity of disease and rate of progression. Electromyographic signs of myopathic changes and spontaneous activity were found in both diseases. Spontaneous activity--bizarre and fibrillation potentials, as well as sharp waves are more common for Duchenne type. The differences between the Becker from Duchenne type of muscular dystrophy can be described on the basis of complex investigations (clinical, electromyographical, histological and biochemical).

Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations.

During a study of hereditary motor and sensory neuropathy-Lom in Bulgaria, a previously unrecognized neurological disorder was encountered, mainly in Wallachian Gypsies, who represent a relatively recent genetic isolate. The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features. Fifty individuals from 19 extended pedigrees were identified and examined clinically and electrophysiologically. At least 1 patient from each family was admitted to the hospital in Sofia for full investigation. Pedigree analysis indicates autosomal recessive inheritance. The disorder is recognized in infancy by the presence of congenital cataracts and microcorneas. A predominantly motor neuropathy beginning in the lower limbs and later affecting the upper limbs develops during childhood and leads to severe disability by the third decade. Associated neurological features are a moderate nonprogressive cognitive deficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature, characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. The CCFDN syndrome is thus a pleomorphic autosomal recessive disorder displaying a combination of neurological and nonneurological features.

Differential diagnosis of chronic idiopathic polymyositis and neuromyositis.

The term neuromyositis indicates a very rare type of polymyositis where, beside the usual muscular manifestations, there are signs of peripheral neuropathy. Although a lot of patients with neuromyositis has been published, it is a very controversial entity. There may be considerable difficulty in distinguishing chronic polymyositis from neuromyositis, even with the aid of electromyographic and muscle biopsy examinations. The aim of this investigation was to re-establish the clues for distinguishing chronic polymyositis from neuromyositis. Fifty-seven patients took part in this investigation. They were subdivided into two groups according to EMG and muscle biopsy data. First group consisted of 29 patients with chronic polymyositis and second group consisted of 28 patients with chronic neuromyositis. Our data confirm the existence of neuromyositis as an entity with different clinical, electromyographic and biopsy findings than polymyositis. The differentiation between chronic polymyositis and neuromyositis is a difficult task on purely clinical ground. Electromyographic recordings with widespread myopathic features, some large potentials and spontaneous activity could be found in both diseases. The most common and important electromyographic findings in patients with neuromyositis are prolonged sensory and motor nerve conduction velocities. In conclusion electromyography and muscle biopsy may be useful in the differential diagnosis of polymyositis and neuromyositis.

Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings.

A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait disorder followed by upper limb weakness in the second decade and, in most subjects, by deafness which is most often first noticed in the third decade. Sensory loss affecting all modalities is present, both this and the motor involvement predominating distally in the limbs. Skeletal deformity, particularly foot deformity, is frequent. Severely reduced motor nerve conduction velocity indicates a demyelinating basis, which was confirmed by nerve biopsy. The three younger patients biopsied showed a hypertrophic 'onion bulb' neuropathy. The hypertrophic changes were not evident in the oldest individual biopsied and it is likely that they had regressed secondarily to axon loss. In the eight cases in which brainstem auditory evoked potentials could be recorded, the results suggested demyelination in the eighth cranial nerve and also abnormal conduction in the central auditory pathways in the brainstem. As no myelin genes are known to be located at chromosome 8q24, the disorder may involve a gene for a novel myelin protein or be due to an abnormality of axon-Schwann cell signalling.

[Features of the type of inheritance of myotonic dystrophy]. / Osobennosti tipa nasledovaniia miotonicheskoi distrofii.

The characteristic features of the genetics of myotonic dystrophy (MD) in the Bulgarian population were studied. Seventy-nine pedigrees were analyzed, comprising a total of 119 patients with MD. The following characteristic features of the MD genetics were revealed: (1) Different families exhibited different patterns of the disease transmission, including vertical (as in the autosomal dominant mode of inheritance), horizontal (as in the autosomal recessive mode of inheritance), and mixed (the horizontal transmission for the first generations and the vertical transmission for the subsequent ones); (2) All studied pedigrees were traced back to clinically healthy ancestors; (3) The symptoms of MD exhibited in anticipation, as well as a clinical heterogeneity in sibships with respect to the severity of the disease. The characteristic features of the revealed mode of inheritance may be explained by dynamic mutations.

Distal muscular dystrophy. Case reports.

The distal muscular dystrophy has been described in 1902 by Gowers. Since then a lot of cases with different mode of inheritance, clinical involvement and morphological findings have been described. Obviously distal myopathies are not a single entity. We describe four new cases of distal myopathy. Although we suppose that they are from the adult-onset Welander's form, they are different in some points. Two cases were with onset in the lower limbs and autosomal dominant inheritance, the third one was sporadic with onset in the lower limbs and the last one was sporadic with onset in the upper limbs. The distal muscles were markedly, while the proximal were slightly involved. Sternocleidomastoid, neck or facial muscles wasting were also found in three cases. The serum creatine kinase in all patients was in nearly normal limits. The electromyographic findings were consistent with chronic myopathy, although fibrillation potentials and positive sharp waves were found in three cases. Muscle biopsy data confirm the myopathic involvement in all patients. We have described patients, which confirm the variability of distal myopathies, regarding the age of onset, initial symptoms, clinical picture, electromyographic and muscle biopsy findings.

Differential diagnosis of scapuloperoneal syndrome.

The nosology of scapuloperoneal syndrome remains controversial. It may be only a stage in the development of facioscapulohumeral dystrophy. The aim of this investigation was to re-establish the clues for distinguishing between scapuloperoneal syndrome and facioscapulohumeral muscular dystrophy. Twelve patients with a scapuloperoneal syndrome were investigated and compared with seventeen patients with facioscapulohumeral dystrophy. The distribution of weakness for both groups of patients was quite different. The electromyographic examination of patients with scapuloperoneal syndrome revealed typical mixed myogenic and neurogenic features and peroneal nerves involvement. The electromyographic findings in patients with facioscapulohumeral muscular dystrophy were typical for myogenic involvement. In conclusion we can suppose that the scapuloperoneal muscular atrophy is not a stage in the development of facioscapulohumeral dystrophy. It is a separate nosological entity with typical clinical and electromyographic findings.

Differential diagnosis of limb girdle syndromes.

The term limb girdle syndrome includes a variety of neuromuscular disorders like the scapulohumeral and pelvifemoral types of muscular dystrophy, quadriceps myopathy and Wohlfart-Kugelberg-Welander syndrome. There may be considerable difficulty in distinguishing between different types of limb girdle syndrome, even with the aid of electromyographic and muscle biopsy examinations. The aim of this investigation was to reestablish the clues for distinguishing between different types of limb girdle syndrome. Fifty-four patients with limb girdle syndromes took part in this investigation. They were subdivided into two groups according to EMG and muscle biopsy data. The first group consisted of 39 patients with limb-girdle type of muscular dystrophy and the second group consisted of 15 patients with juvenile type of spinal muscular atrophy. Our results revealed that neurological examination was not enough to distinguish the different types of limb girdle syndrome. The most important electromyographic findings in patients with muscular atrophy are the neurogenic action potentials and fasciculations. Fibrillations, positive sharp waves and bizzare discharges may be found also in some patients with muscular dystrophy. Myogenic action potentials are found in some patients with muscular atrophy and so may cause confusion. Muscle biopsy may also reveal some myogenic features in patients with muscular atrophy. In conclusion electromyography and muscle biopsy are useful in the differentiation of different types of limb girdle syndrome, as well as, in determining the exact pattern of muscle involvement.

Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24.

Founder effect and linkage disequilibrium have been successfully exploited to map single gene disorders, and the study of isolated populations is emerging as a major approach to the investigation of genetically complex diseases. In the search for genetic isolates ranging from Pacific islands to Middle East deserts, the 10 million Gypsies resident in Europe have largely escaped the attention of geneticists. Because of their geographical ubiquity, lack of written history and the presumed social and cultural nature of their isolation, Gypsies are construed as not meeting the criteria for a well defined founder population. Gypsy society has a complex structure with subdivisions and stratifications that are incomprehensible to the surrounding populations. Marginalization by the health care systems in most countries results in a lack of information on causes of morbidity and mortality and little is known about hereditary disorders or the population genetic characteristics of Gypsies. This study is the first example of mapping a disease gene in endogamous Gypsy groups. Using lod score analysis and linkage disequilibrium, we have located a novel demyelinating neuropathy to a narrow interval on chromosome 8q24. We show that the disease, occurring in Gypsy groups of different identity and history of migrations, is caused by a single mutation whose origin predates the divergence of these groups.

Schwartz-Jampel syndrome: clinical, electromyographic and genetic studies.

Two sisters aged 9 and 7 from consanguineous parents are described. Both of them develop myotonia, muscular weakness as early as the first year after birth. At the age 3-4 a disturbed gait appeared due to knee joint contractures and limited joint movements. The children display facial dysmorphism (a small forehead, a flat base of the nose, a receding chin, an irregular order of the teeth, low-set ears, a high-arched palate, low hair-line), kyphoscoliosis, pigeon breast, severe contractures of the knee and elbow joint and foot deformities. The elder sister cannot walk. Hirsutism of all four limbs is found as well as sparse subcutaneous tissue. Muscles are stiff and firm. Tendon reflexes of the lower limbs are absent. Muscle enzymes show slightly increased values. The EMG needle examination in both sisters was abnormal. Spontaneous, continuous, high-frequency, low-voltage electrical discharges were observed in all distal and proximal muscles of the hands and legs. Some of them have a typical myotonic pattern. The MCV and the SCV was within the normal range. Both parents of our patients, their sister aged 4, as well as their grandparents showed no clinical and EMG abnormalities. All these data allow authors to affirm the diagnosis chondrodystrophic myotonia., described for the first time in Bulgaria.