[Mitochondrial respiratory chain diseases. Evaluation and variability in 52 patients]. / Enfermedades de la cadena respiratoria mitocondrial. Evaluación y variabilidad en 52 pacientes.

INTRODUCTION: Clinical, electrophysiological, genetic and biochemical deficiencies variability were evaluated in 52 patients diagnosed of mitochondrial respiratory chain diseases (MRCD). PATIENTS AND METHODS: 26 men and 26 women, aged 19 to 79 years, were tested by clinical examination, electrophysiological techniques, muscle biopsy and genetic and biochemical studies. RESULTS: The patients were classified into seven phenotypes: myopathy, chronic progressive external ophthalmoplegia, progressive ophthalmoplegia plus ataxia, Kearns-Sayre syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke episodes (MELAS), myoclonic encephalopathy with ragged-red fibers (MERRF), and encephalopathies. Each phenotype may begin by different ways. The electromiography showed myopathy in 39 cases and various types of neuropathy in 10. Ragged-red COX negative fibers or widespread electron microscopic abnormalities were found in 47 cases. Simple deletions, multiple deletions and three different point mutations were observed. Deficiency of complexes I, II, III and IV were found alone or in different associations. CONCLUSIONS: MRCD shows wide variations in clinical, genetic and biochemical studies. Some patients with nonspecific manifestations, mainly of central nervous system, need careful attention and to be on account of diagnostic suspicion.

Abnormal sensory nerve conduction in multifocal demyelinating neuropathy with persistent conduction block.

Two patients exhibited chronic, slightly asymmetric weakness and wasting with fasciculations of the upper limb and hand muscles. Motor nerve conduction studies showed features of multifocal conduction block in nerve segments other than those usually involved in entrapment syndromes. The F wave was markedly delayed in the median and ulnar nerves. Transcranial cortical and cervical root magnetic stimulation showed bilaterally delayed thenar responses with normal central conduction time. Needle electromyography demonstrated a chronic denervation pattern with large polyphasic motor units in several muscles of the upper limbs. Sensory symptoms were mild and limited to paresthesias in the fingertips. Sensory nerve conduction velocity and sensory nerve action potential amplitudes were normal in elbow-to-wrist and wrist-to-finger segments of the median and ulnar nerves, but there was a delayed cortical response and unrecognizable Erb's point and cervical responses in the somatosensory evoked potentials to median nerve electrical stimulation. Electrophysiologic examination was normal in most nerves of the lower limbs. These two patients, meeting clinical and electrophysiologic criteria of multifocal neuropathy with conduction block, demonstrate that sensory fibers may also be involved in this syndrome.

IgG anti-ganglioside antibodies and their subclass distribution in two patients with acute and chronic motor neuropathy.

IgG anti-ganglioside antibodies were found in two patients with motor neuropathy. The first patient had a chronic axonal neuropathy with persistently elevated anti-GM1 antibodies. The second patient had an acute axonal neuropathy with anti-GM1, GD1b and asialoGM1 antibodies. In both, the IgG subclass study showed that the antibodies belonged to the IgG1 subclass. An enzyme-linked immunosorbent assay (ELISA) for light chains revealed anti-ganglioside antibodies of the lambda type.

Phrenic nerve conduction study in demyelinating neuropathies and open-heart surgery.

OBJECTIVES: The aim of this study was to determine normal values of phrenic nerve conduction (PNC) in healthy individuals; to evaluate the subclinical extent of phrenic nerve involvement in Guillain-Barré syndrome (G-B) and hereditary motor and sensory neuropathy-I (HMSN-I), and to evaluate phrenic nerve damage after cardiac surgery. MATERIALS AND METHODS: PNC was performed by transcutaneous stimulation in the neck and recording the diaphragmatic potential from surface electrodes placed at the seventh and eight intercostal spaces. PNC was performed bilaterally in 25 healthy volunteers and 25 patients before and after open-heart surgery. Right PNC was also performed in 5 cases with G-B and 5 patients with HMNS-I. RESULTS: Latency and amplitude of the diaphragmatic potential were the same in controls and in patients with cardiac disease before surgery. After surgery, 28% of patients had left phrenic nerve inexcitability, and 8% had reduced amplitude of the response. These 9 patients demonstrated elevation of the left hemidiaphragm on chest radiography. Left PNC performed 1 year after the operation showed improvement in latency and amplitude of the responses in all except one patient. PNC was prolonged in 4 out of 5 cases with G-B and in all patients with HMNS-I. CONCLUSIONS: PNC is an easy and reliable method in evaluating phrenic nerve damage due to hypothermia or primary stretch injury in patients after cardiac surgery. PNC may be helpful in detecting diaphragmatic involvement before clinical ventilatory insufficiency in demyelinating neuropathies such as G-B and HMNS-I.

[Multifocal polyneuropathy with persistent conduction blockage. A new subset of chronic inflammatory polyneuropathies]. / Polineuropatía multifocal con bloqueos de conducción persistentes. Un nuevo subgrupo dentro de las polineuropatías inflamatorias crónicas.

Recently a subset of chronic demyelinating inflammatory polyneuropathies with asymmetrical involvement limited to upper limbs, at least at the onset, resembling a multifocal mononeuropathy has been described. Electrodiagnostic testing disclosed multifocal CB outside the common entrapment sites has been described. We report a 55 years old man with a 4 years history of paresis, numbness, fasciculations, myokymia, cramps and mild amyotrophy. Electrophysiological evaluation showed proximal multifocal conduction block and abundant spontaneous activity as fasciculations, myokymia and scarce denervation activity. The importance of taking into account this entity in the differential diagnosis of patients with suspected mononeuritis multiplex or motoneuron disease is emphasized. The nosologic place of this entity is also discussed.

Conduction velocity along muscle fibers in situ in myasthenia gravis.

The muscle fiber conduction velocity (MFCV) was tested distally in the short head of the biceps brachii muscle in 4 patients with ocular and 16 cases with generalized Myasthenia Gravis. The mean MFCV was decreased in 6 cases with generalized form of the disease, 2 of them with short evolution of the symptoms and without drugs therapy. The overall MFCV of 644 fibers in generalized MG was significantly decreased (p < 0.02) related to the results of controls. The MFCV is an index of the muscle fiber size. Muscle fiber atrophy in MG may be due to functional denervation in patients without drugs therapy or to motor neuropathy caused by drugs or associated with thymoma.

Conduction velocity in human muscle fibers in situ. Study in upper and lower limbs in healthy adults.

The muscle fibers of the human biceps brachii and vastus medialis muscles were stimulated with low voltages in their distal portion by means of monopolar needles in 50 healthy adults. The electrical activity was recorded proximally by means of a SFEMG electrode. The conduction velocity of the muscle fibers in situ calculated with this method had a Gaussian distribution for both muscles, showed values slightly higher in males than in females, did not decrease significantly with ageing, and was significantly related to limbs perimeter. The recorded potentials and their propagation velocity were the same before than after curarization. The possible interest of the method for testing the muscle fiber function and size in pathological conditions of the nerve and muscle is suggested.

Peripheral nerve conduction and central motor conduction after magnetic stimulation of the brain in myotonic dystrophy.

Central motor conduction time was calculated after magnetic stimulation of the brain in 15 patients with myotonic dystrophy and in 38 healthy voluntaries of the same age. Conventional electromyography and motor and sensory conduction velocities were also performed. Central motor conduction time from vertex to C8 was within the normal range in all patients whereas motor conduction velocity of the peripheral nerve and amplitude of the nerve evoked potentials were slightly reduced in 3 and 2 cases respectively, supporting peripheral nerve involvement in some subjects. Our results suggest that the reported central nervous system involvement in myotonic dystrophy, including the nonspecific white matter lesions showed by magnetic resonance imaging, would not affect the conduction of the corticospinal tracts. Magnetic stimulation on the motor cortex is a painless method to study the central nervous system and apports a satisfactory approximation to central motor pathways conduction.

Electrophysiological assessment in neurogenic thoracic outlet syndrome.

OBJECTIVES: To evaluate the value of different electrophysiological techniques in the diagnosis of neurogenic thoracic outlet syndrome (TOS). MATERIALS AND METHODS: Two females, aged 22 and 30 years, with progressive weakness and wasting of the right hand with slight sensory disturbances. Needle EMG, motor and sensory conduction along median and ulnar nerves, sensory conduction of medial (MACN) and lateral (LACN) antebrachial cutaneous nerves. RESULTS: Chronic neurogenic atrophy in small hand muscles, more severe in lateral part of thenar eminency, reduced compound muscle action potentials (CMAPs) more severe by median than ulnar stimulation, and reduced amplitude of the SNAPs of ulnar and MACN were the main findings consistent with neurogenic TOS. Both patients had right cervical rib in radiography. CONCLUSIONS: Electrophysiological study is useful in the diagnosis of neurogenic TOS. Reduced amplitude of MACN and ulnar nerve SNAPs, predominant denervation in thenar eminency, and reduced amplitude of CMAPs, more by median than by ulnar stimulation, are consistent with the diagnosis.

Electrophysiologic study in peripheral neuropathy associated with HIV infection.

Clinical and electrophysiologic features in 22 patients with HIV infection are reported. Four cases had chronic demyelinating polyneuropathy, two mononeuropathy multiplex, and nine symmetrical sensory-motor polyneuropathy. Seven cases had normal clinical and electromyographic examination. Electrophysiological study had a higher diagnostic yield (68%) than clinical examination (50%) for peripheral neuropathy diagnosis. Thus, peripheral nerve abnormalities are frequent in patients with different stages of HIV infection, although their pathogenesis remains unclear. Symmetrical sensory-motor polyneuropathy is the main type of neuropathy seen in ouvert AIDS, whereas chronic demyelinating polyneuropathy was mainly diagnosed in patients with asymptomatic HIV infection as first manifestation of the disease. Axonal or demyelinating nerve damage was established according to electrophysiological criteria. Frequently a mixture of both lesions was found. Electrophysiologic study is also a good index of neuropathy evolution in HIV infection and to follow-up of nerve abnormalities after treatment.

Follow-up study after replantation of the forearm and nerves resuture.

OBJECTIVE: Clinical and electrophysiological evolution after total section of the forearm and nerves resuture. MATERIAL AND METHODS: A young boy aged 14 years with accidental amputation of the right forearm. The forearm was replanted within the first 6 hours after accident. Electromyography, nerve conduction, estimated number of the motor units, single fiber EMG and motor complex reflex responses were studied until 4 years after surgery. RESULTS: Functional recovery was reached in muscles innervated by median and ulnar nerves. After 4 years of evolution EMG showed signs of chronic neuropathy. Nerve conduction did not reach normal values. Single fiber EMG showed increased fiber density and jitter, and intermittent impulse blocking The estimated number of the motor units was severely reduced with high mean amplitude. Motor reflex responses were elicited by cutaneous stimulation consistent with axon reflexes or ephatic responses. CONCLUSIONS: Replanted limbs in selected cases and nerve's resuture may reach a functional recovery for daily activities.

Central motor conduction in hereditary motor and sensory neuropathy and hereditary spastic paraplegia.

Conduction of the central motor pathways (CMCT) by magnetic stimulation of the motor cortex (TMS) was performed in 17 patients with hereditary motor sensory neuropathy (HMSN) and 2 siblings with hereditary spastic paraplegia (HSP). CMCT was prolonged in two patients with HMSN I with associated pyramidal features and in two subjects with HMSN II without clinical pyramidal signs. CMCT may be abnormal in HMSN due to central motor pathways involvement or altered spinal excitability with increased synaptic delay. CMCT was normal in the upper limbs in patients with HSP but increased in the legs. Diagnostic yield of TMS increased in less disabled cases with HSP when selective conduction at the spinal level (C7-S1) was calculated. Abnormal spinal conduction in HSP is consistent with degeneration of the crossed corticospinal tracts at the thoracic level found in neuropathologic observations.

Transcranial magnetic stimulation in amyotrophic and primary lateral sclerosis.

Conduction of the central motor pathways after transcranial magnetic stimulation (TMS) was investigated in 7 patients with amyotrophic lateral sclerosis (ALS) and 1 case with primary lateral sclerosis (PLS). Threshold intensity, central motor conduction time (CMCT) and amplitude of the motor evoked potentials (MEPs) were evaluated. Threshold was abnormal in 85% of tested limbs, and CMCT prolonged and amplitude of the MEPs attenuated in 28.5% of patients with ALS. Abnormal CMCT was asymmetric and related to clinical score. MEPs were absent in lower limbs in PLS, with prolonged or attenuated amplitude of the MEPs in upper limbs. EMG showed widespread signs of lower motor neuron involvement in ALS, but not in PLS. Cranial MRI showed frontoparietal cortical atrophy, more marked in pre-central gyrus, and SPECT there was lower tracer uptake in the perirolandic area in the PLS patient. EMG examination, TMS, cranial MRI and SPECT can help in the diagnosis of PLS.

Motor unit remodelling in Duchenne muscular dystrophy. Electrophysiological assessment.

Conventional EMG, motor and sensory conduction velocities, averaging analysis of MUPs, SFEMG, and muscle fiber conduction velocity in situ were performed in 14 boys with Duchenne muscular dystrophy (DD) aged 5 to 11 years. MUPs parameters study showed a striking increment of long duration MUPs followed by satellites and increase of polyphasic potentials of variable duration. The main findings in SFEMG examination were increment in fiber density of the motor unit, large MISI and presence of complex potentials of long duration in all patients. Muscle fiber conduction velocity in situ was significantly slower than in controls, with significant decrease in minimum conduction and increased variability (large SD) in propagation velocity values. Low conduction velocity of muscle fibers, long duration of polyphasics and MUPs followed by satellites, and large MISI were significantly related. These findings support the hypotheses which have suggested that the motor unit remodelling in DD is mainly myogenic. The abnormalities in muscle fiber conduction velocity in situ reflect an increased diameter variation of muscle fibers consistent with splitting fibers, small groups of regenerating and necrotic fibers, and fiber diameter variation found in histological studies. Thus, increased variability in fiber diameter may be the cause of complex and long duration MUPs in DD.

Somatosensory evoked potentials and central motor pathways conduction after magnetic stimulation of the brain in diabetes.

Somatosensory evoked potentials (SEPs) on stimulating median and posterior tibial nerves, and central and spinal conduction time of the motor pathways calculated by means of magnetic stimulation of the cortex were valuated in diabetic patients. The latencies L1-Cortex and L1-C7 were significantly larger in 54 diabetics than in controls. An increment in L1-C7 interval was found in 17 patients, and the latency L1-Cortex was increased in 20. No patients showed increase in C7-Cortex interval. The increased latency L1-C7 reflects a delayed conduction along afferent spinal pathways in some patients with diabetes in contrast with the normal C7-Cortex supraspinal segment. The central and spinal conduction time after magnetic stimulation of the cortex were normal in 14 out of 15 tested diabetics suggesting that central motor pathways were spared. These results are consistent with the existence of a central-peripheral sensory axonopathy in some diabetics.

Electrophysiologic evaluation of Emery-Dreifuss muscular dystrophy. A single fiber and quantitative EMG study.

A 16-year-old boy, the only affected member of the family, noticed early onset contracture of the elbows, and developed slowly progressive humeroperoneal weakness and atrophy, and bilateral equinus. The severe restriction of the forward flexion of the neck and thoracolumbar spine, resembled a rigid spine syndrome. An electrocardiogram showed atrioventricular conduction abnormalities. Muscle biopsy was consistent with mild myopathy. The overall conventional findings of a detailed electromyographic study in the limbs and erector trunci muscles, as well as the results of conduction velocity, automatic analysis of the voluntary pattern and single fiber electromyography studies were consistent with myopathy, although some atypical findings were found. The controversy about neurogenic and myopathic features in Emery-Dreifuss disease is discussed. The unspecific value of the flexion limitation of the spine, and the uncertain nosological position of the rigid spine syndrome are also commented.

Conduction velocity along muscle fibers in situ in healthy infants.

The muscle fibers of the biceps brachii were stimulated distally with low voltages by means of two monopolar needles in twenty-two infants aged 2 to 14 years. The electrical activity was recorded proximally by means of a SFEMG electrode. Conduction velocity of the muscle fibers (MFCV) in situ calculated with this method had a bimodal distribution in the youngest individuals of less than 4 years, and a Gaussian distribution in children aged 5 to 14 years. Propagation velocity along muscle fibers increases with children's age and is significantly slower than in adults, in good correlation with the shorter limb perimeter and with the significantly smaller fiber diameter found in muscle biopsies in infancy. The latency of the evoked potentials was linearly related with the distance between stimulating and recording points, and muscle activity and propagation velocities were the same before and after curarization, that is consistent with the reliability of the method in infancy.

The muscle inhibitory period by transcranial magnetic stimulation. Study in stroke patients.

Motor evoked potentials (MEPs) elicited over hand muscles by transcranial magnetic stimulation (TMS) were studied in healthy individuals and, bilaterally, in patients with cerebral infarction. Conduction time of the central motor pathways (CMCT), threshold intensity, and amplitude of the MEPs were correlated with recovery motor hand function after stroke. Following MEPs by TMS during tonic muscle contraction, there is a transient suppression of muscle action. This inhibitory period (IP) was significantly shorter in the upper paretic limb of stroke patients with spasticity than in normal limb of the patients and healthy individuals. Shortening of the IP duration was correlated to degree of upper limb spasticity (Ashworth scale) and may be due to supraspinal level reduction of the inhibitory function. The IP study contributes to a better quantification of the hand function in stroke patients.

Motor hand recovery after stroke. Prognostic yield of early transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was performed in 20 patients within the first days after stroke. Motor evoked potentials (MEPs) were bilaterally recorded over thenar eminence muscles, and central motor conduction time (CMCT), amplitude of the MEPs (A%M) and threshold intensity compared between both sides. Six months later the patients were reexamined. Within the first days after stroke the obtention of MEPs at rest or during voluntary muscle activation have a favorable prognostic value. All patients with early response by TMS reached a good motor function in the following months. The follow-up showed that the electrophysiological improvement was closely related to clinical recovery of the hand function. However, even in cases with a good recovery, the CMCT and, mainly, the A%M, may be significantly different related to those in normal hand. TMS may be an early and valuable prognostic indicator of hand function recovery after stroke, and their prognostic yield is higher than clinical evaluation and CT study. TMS is a quantifiable method of motor disability and may have practical application in the management and rehabilitation therapy in stroke patients.

Chronic inflammatory demyelinating polyneuropathy as first manifestation of human immunodeficiency virus infection.

We studied three patients who were admitted to the hospital because of progressive weakness without other systemic signs or symptoms. All three cases were young males who had been intravenous drug user for many years. Electrophysiologic study showed prolonged distal latencies and marked slowing of motor and sensory conduction velocities, consistent with primary demyelination. Nerve biopsy also showed signs of demyelination. Antibodies against HIV in CSF and blood were detected during the diagnostic evaluation. Clinical and electrophysiological studies improved in two cases after prednisone administration. Patients with predominant motor demyelinating neuropathies and risk factors should be screen for HIV infection.