Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in the muscles of patients with long-standing denervation (postpoliomyelitis muscular atrophy): similarities with inclusion body myositis

In the chronically denervated muscles of patients with prior paralytic poliomyelitis, there are secondary myopathic features, including endomysial inflammation and rare vacuolated fibers. To assess the frequency and characteristics of the vacuoles and their similarities with those seen in inclusion body myositis (IBM), we examined 58 muscle biopsy specimens from patients with prior paralytic poliomyelitis for (1) the presence of rimmed vacuoles; (2) acid-phosphatase reactivity; (3) Congo-red-positive amyloid deposits; (4) electron microscopy, searching for tubulofilaments; and (5) immunoelectron microscopy, using antibodies against beta-amyloid and ubiquitin. We found vacuolated muscle fibers in 18 of 58 (31%) biopsies, with a mean frequency of 2.06 +/- 0.42 fibers per specimen. The vacuoles contained acid phosphatase-positive material in 6 of the 18 (33.30%) specimens and stained positive for Congo red in five (27.80%). By immunoelectron microscopy, the vacuoles contained 5.17 +/- 0.13 nm fibrils and 14.9 +/- 0.31 nm filaments that immunoreacted with antibodies to beta-amyloid and ubiquitin in a pattern identical to the one seen in IBM. We conclude that vacuolated muscle fibers containing filamentous inclusions positive for amyloid and ubiquitin are not unique to IBM and the other vacuolar myopathies but can also occur in a chronic neurogenic condition, such as postpoliomyelitis. The chronicity of the underlying disease, rather than the cause, may lead to vacuolar formation, amyloid deposition, and accumulation of ubiquitinated filaments.     

The prevalence of Helicobacter pylori-positive serology in asymptomatic children

Surgeons frequently perform sural nerve biopsy as part of the work-up of patients with peripheral neuropathy. The indications for the procedure, therapeutic value, and complications associated with the procedure have received little attention in the surgical literature. A retrospective chart review of 60 patients with the suspected diagnosis of peripheral neuropathy undergoing sural nerve biopsy was performed. Vasculitis was suspected in 29 (48%) patients undergoing biopsy. This diagnosis was confirmed in 6 of the 29 patients and resulted in the alteration of therapy in 31% of patients with this suspected diagnosis. In 27 (45%) patients, the etiology of their peripheral neuropathy was unknown. Twelve (44%) patients in this group had sural nerve pathology; however, no change in therapy was required. Ten patients in our series had associated malignant tumors; some of these patients were diagnosed after referral for sural nerve biopsy. Twenty-five (42%) patients remained undiagnosed after biopsy. Nerve conduction studies were performed in 14 (22%) patients. Thirteen patients with abnormal lower extremity nerve conduction studies had 6 normal and 7 abnormal biopsy results. The one patient with a normal study had a normal nerve biopsy result. There were six (10%) patients with wound infections, seven (12%) patients with delayed wound healing, and three (5%) patients with new onset of chronic pain in the distribution of the sural nerve, for an overall complication rate of 27%. There was no correlation between the preoperative use of antibiotics, type of local anesthetic used, or length of nerve excised and complication rate. We conclude that the complication rate after sural nerve biopsy is significant. Strict criteria should be employed in selecting patients for sural nerve biopsy including a careful neurologic history and physical examination, nerve conduction studies, appropriate work-up for vasculitis if suspected, and implementation of a search for malignancy if this is not apparent. If the diagnosis is still in question, then sural nerve biopsy would seem appropriate, especially in patients with suspected vasculitis.     

Chronic inflammatory demyelinating polyradiculoneuropathy. Study of 18 cases

This is a prospective study that describes 18 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic type. The patients have been followed for a period of 4 to 127 months. We evaluated the clinical characteristics, the evolution, and therapeutic response. Male patients outnumbered female patients in a proportion of 1.25:1. Symptoms first appeared at an age ranging from 6 to 85. Most of the patients denied the occurrence of preceding events and a progressive evolution prevailed over relapsing evolution. All patients had both motor and sensory dysfunction associated with loss of tendon reflexes, and only three patients (16.7%) had cranial nerve involvement. The cerebrospinal fluid protein levels were increased in 88.9% of the patients and mean level was 203.4 mg/dl. Electrophysiological studies revealed demyelination in all patients and axonal damage in 94.4%. Preponderant characteristics in the sural nerve biopsy of seven patients showed demyelination and remyelination, and changes indicative of axonal damage were often present. The anti-HLA Dr antibodies were found in the sural nerve of one patient and anti-CD3 antibodies in the sural nerve of two. All patients were first treated with prednisone. The drug was maintained in reduced doses and given in alternate days to 72.2% of the patients with success. Two patients (11.1%) are asymptomatic even after the withdrawal of all medication. We administered azathioprine, associated or not with corticoid, to the four patients who had not had a satisfactory response to the prednisone treatment. By the time of the last evaluation 16 patients (88.9%) had functional improvement.     

Muscular ultrasound in idiopathic inflammatory myopathies of adults

To evaluate the value of myosonography in inflammatory myopathies ultrasound of skeletal muscles was performed in 70 patients, aged 21-82 years, suffering from histologically proven polymyositis (n = 30), dermatomyositis (n = 18), granulomatous myositis (n = 9), inclusion body myositis (n = 13), and in 102 control persons. The sensitivity of muscle ultrasound in detecting histopathologically proven disease (82.9%) was not significantly different from electromyography (92.4%) or serum creatine kinase activity (68.7%). The positive predictive value of ultrasound was 95.1%, the negative predictive value 89.2%, and the accuracy 91.3%. The different types of inflammatory myopathies presented with typical, but not specific ultrasound features. Polymyositis showed atrophy and increased echointensity predominantly of lower extremity muscles, whereas in dermatomyositis clear muscle atrophy was rare and echointensities were highest in forearm muscles. Echointensities were lower in dermatomyositis compared to poly- and granulomatous myositis. Granulomatous myositis was characterized by the highest echointensities and a tendency towards muscle hypertrophy. Severe muscle atrophy was the most impressive feature in the majority of patients with inclusion body myositis. Comparison of ultrasound and histopathological findings indicates that muscle lipomatosis has a much greater impact on muscular echointensity than does muscle fibrosis. Ultrasound of myositis improved clinical assessment of patients by supplying differential diagnostic clues based on precise muscle size measurements and identification of mesenchymal abnormalities, particularly muscle lipomatosis.     

Diagnosis of acute intermittent porphyria in northern Sweden: an evaluation of mutation analysis and biochemical methods

Pathology of the primary sensory neurons was examined in 7 autopsied patients and 6 biopsied sural nerves from the patients with X-linked recessive bulbospinal neuronopathy (SBMA). Large myelinated fibers in the central rami (L-4 posterior root, L-4, T-7, and C-6 segment of the fasciculus gracilis), and in the peripheral rami (sural nerve) were diminished in a distally accentuated manner, while small myelinated and unmyelinate fibers were well preserved in number. Demylinating process and axonal atrophy was ubiquitous. The diameter frequency histograms of the dorsal root ganglion (DRG) neurons showed a decrease in the number of large diameter neurons and an increase in the number of small diameter neurons without substantial loss of whole number of neurons, which suggested that neuronal size was atrophied. These data suggested central and peripheral distal axonopathy with neuronal atrophy was the process of sensory neuron involvement. Expression of mutant androgen receptor mRNA with elongated CAG repeat in the DRG and sural nerve supported the view that sensory nerve involvement is the primary process in SBMA.     

The effect of bipolar electrocautery on peripheral nerves

Although bipolar cautery was designed to minimize trauma to the central nervous system, little is known about the effects of bipolar cautery on peripheral nerve tissue. This experiment was designed to study the effect of direct bipolar cautery on a peripheral nerve and the muscles innervated by that nerve. Lewis rats (n = 200) were assigned to five different groups: control, sham, and three cautery groups (duration of either 0.5, 1.0, or 1.5 seconds). The hind limb tibial nerves were isolated in the sham group and isolated and cauterized in the cautery groups. Assessments performed at 2 hours, 2 weeks, 4 weeks, and 8 weeks postoperatively included isometric contractile function studies of both a fast- and a slow-twitch muscle, muscle weights, and nerve histology/morphometry. Significant muscle weight loss and reduced muscle function were found in the cautery groups at 2, 4, and 8 weeks (p < 0.05). Histologically, the nerves of the cautery groups showed nerve damage consistent with Sunderland's type 4 nerve injury when examined at 2 weeks and showed nerve regeneration at 4 and 8 weeks. Both the fast-twitch muscle and the shorter duration cautery were associated with faster recovery relative to the slow-twitch muscles and longer duration cautery, respectively. Bipolar cautery, as administered to rat tibial nerves in this experiment, is associated with a significant injury to the nerve and loss of function of the muscles innervated by the nerve.     

Peripheral nervous system involvement in human and experimental chronic American trypanosomiasis

An electrophysiological and histological study of the muscle and the peripheral nervous system (PNS) was carried out in chronic human American trypanosomiasis (Chagas' disease) and in an experimental Chagas' disease (Chd) mouse model. Altogether 995 patients with chronic Chd and 261 mice, experimentally infected with RA and CA-I parasite strains, were investigated. Results were compared with matched controls. Techniques employed in humans were: clinical assessment, conventional electromyography (EMG), estimated number of motor units, motor and sensory nerve conduction velocities, repetitive nerve stimulation and muscle and sural nerve biopsies. In mice conventional EMG, sciatic nerve conduction time, sciatic nerve action potential amplitude, in vitro miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) recordings, muscle, nerve and spinal cord histology and identification of cell phenotypes within the inflammatory infiltrates were the employed procedures. Out of 511 patients submitted to clinical examination, 52 disclosed signs and symptoms of mixed peripheral neuropathy. By employing electrophysiological techniques, it could be shown that about 30% of the investigated patients had one or more of the following features: diminished interference pattern, most of the remainder motor unit potentials being (MUPs) polyphasic; reduced number of functional motor units in the thenar, hypothenar, soleus and/or edb muscles; slow sensory and motor nerve conduction velocities; low sensory action potential amplitude and impairement of neuromuscular transmission. In mice, MUPs duration and amplitude were increased at later stages of the infection, nerve conduction was slow, nerve action potentials were of low amplitude, mepps were of low amplitude and double epps were frequently found. Muscle histology in humans with chronic Chd showed type I and type II grouping, atrophic angular fibers and targetoid muscle fibers. In mice perivascular mononuclear cells infiltrates, small round fibers, muscle fibers necrosis, atrophic angular fibers, type II muscle fibers grouping and grouped muscle fibers atrophy were found. Sural nerve samples showed segmental and paranodal demyelination and axonal loss. The same features were observed in mice nerves, also in this model mononuclear cells infiltrates at the nerve, dorsal root ganglia and meninges surrounding the spinal cord were observed. Muscle and nervous tissues infiltrates were mainly composed of T lymphocytes with predominance of CD8 or CD4 subsets according to the parasites strain employed for infecting the animals. These findings suggest that the skeletal muscle and the PNS may be involved in chronic American trypanosomiasis.     

Acute brachial neuritis (Parsonage-Turner syndrome): MR imaging appearance--report of three cases

Magnetic resonance (MR) imaging findings in three patients with acute onset of neuritic shoulder pain and weakness included high signal intensity in supra- and infraspinatus muscles (n = 2), partial involvement of infraspinatus muscle (n = 1) and of deltoid muscle (n = 1), and atrophy of supra- and infraspinatus muscles (n = 2). Clinical diagnosis of acute brachial neuritis (Parsonage-Turner syndrome) correlated with MR imaging results in all cases.     

Motor-unit recruitment in self-reinnervated muscle

1. Recruitment order of motor units in self-reinnervated medial gastrocnemius (MG) muscles was studied in decerebrate cats 16 mo after surgical reunion of the cut MG nerve. Pairs of MG motor units were isolated by dual microelectrode penetration of ventral roots to measure their recruitment sequence during cutaneous reflexes in relation to their physiological properties. 2. Physiological properties of reconstituted motor units appeared normal, as expected. Also normal were the relationships among these properties: twitch and tetanic tension tended to increase with axonal conduction velocity and decrease with twitch contraction time. A small fraction of motor units (10/116) in reinnervated muscles produced either no measurable tension or unusually large amounts of tension compared with controls. This was the only distinct feature of the sample of reconstituted units. 3. In muscles reinnervated after nerve section, stretch was notably ineffective in eliciting reflex contraction of MG muscles or their constituent motor units (only 5/116 units). Incomplete recovery from nerve section was probably the cause of this impairment, because stretch reflexes were readily evoked in adjacent untreated muscles and in one reinnervated MG muscle that was studied 16 mo after nerve crush. In contrast with the ineffectiveness of muscle stretch, sural nerve stimulation succeeded in recruiting 49/116 units, a proportion fairly typical of normal MG muscles. 4. The contractions of the first unit recruited in cutaneous reflexes tended to be slower and less forceful than those of the other unit in a pair. By these measures, recruitment obeyed the size principle. This recruitment order with respect to unit contractile properties was not significantly different (P > 0.05) between untreated and reinnervated muscles but was significantly (P < 0.005) different from random order in both groups. The same recruitment pattern was observed for pairs of motor units sampled from the muscle reinnervated after nerve crush, whether units were recruited by muscle stretch or sural nerve stimulation. 5. The usual tendency for motor units with slower conduction velocity (CV) to be recruited in sural nerve reflexes before those with faster CV was not strong in reinnervated muscles. After nerve section the proportion of units exhibiting the usual recruitment pattern was not significantly different (P > 0.05) from a random pattern for CV. 6. The central finding is that the normal recruitment patterns recover from nerve injury in a muscle that is reinnervated by its original nerve. By contrast, stretch reflexes do not recover well from nerve section, and this deficiency may contribute to motor disability.     

Hereditary motor and sensory neuropathy with calf hypertrophy is associated with 17p11.2 duplication

The demyelinating type of hereditary motor and sensory neuropathy (HMSN I) is characterized by progressive weakness and atrophy of leg muscles. Six patients (age, 25-79 yr) belonging to three generations had calf hypertrophy (6 of 6), foot drop or difficulty with heel walking (4 of 6), pes cavus (3 of 6), absent or depressed tendon jerks in the lower limbs (4 of 6), and mild distal sensory loss (3 of 6). No other family member had leg atrophy. Motor conduction velocities ranged from 20 to 40 m/sec. Sural nerve biopsy showed loss of large myelinated fibers, numerous onion bulbs, and segmental demyelination and remyelination. Computed tomographic scans of leg muscles and histological and morphometric findings in gastrocnemius revealed true muscular hypertrophy. Southern blot and fluorescence in situ hybridization documented the duplication of the entire 17p11.2 segment associated with classical HMSN IA. The pathogenesis of muscle hypertrophy in our cases is unclear. Chronic leg muscle weakness and long-standing partial denervation might cause calf enlargement by a combination of compensatory "work-induced" and "stretch-induced" fiber hypertrophy. Alternatively, that all the affected family members presented calf hypertrophy might suggest the action of a genetic factor associated with the duplication at 17p11.2.     

Comparing the behavior of children treated using general anesthesia with those treated using conscious sedation

The histopathologic study was performed to elucidate whether the fiber type atrophy of the vastus lateralis muscle in patients with hip or knee joint disorders is related to the activities of daily living (ADL) or habitual physical activity. Subjects were 16 female patients, 52.4 +/- 16.0 yr of age (mean +/- standard deviation), who underwent a vastus lateralis muscle biopsy at the time of total hip or knee replacement. At the time of referral to the rehabilitation center, the Functional Independence Measure (FIM) motor score and habitual physical activity at home were evaluated, and the diameter and atrophy factor for each muscle fiber type were measured on the histopathologic preparations of the biopsied muscles. The data were analyzed using ttest, one-way analysis of variance (ANOVA), Kruskal-Wallis one-way ANOVA, Spearman's correlation coefficient, and partial correlation coefficient. The patients showed muscle fiber atrophy and small angular fibers, and the atrophy factor was significantly increased in type 1, 2A, and 2B fibers, in that order (one-way ANOVA, P < 0.05). The patterns of the fiber type atrophy, consisting of normal, type 2B atrophy, type 2AB atrophy, and type 1 and 2AB atrophy, had a significant relationship with the fiber type atrophy (Spearman's correlation coefficient; rho = 0.834, P < 0.001). The FIM motor score showed a significant correlation with the atrophy factor (r = -0.584, P < 0.05), and significant differences were recognized among the four patterns of the fiber type atrophy (Kruskal-Wallis one-way ANOVA, P < 0.05). In conclusion, the muscle atrophy and patterns of the fiber type atrophy of the vastus lateralis muscle in patients with joint disorders may be related to changes in the FIM motor score.     

A family with neurogenic atrophy of the distal muscles of the upper limbs: clinical and electrophysiological studies

A Chinese family manifested mild neurogenic atrophy of the distal muscles of the upper limbs. None of the affected members had sensory abnormalities, or pyramidal tract or bulbar involvement. The onset of the illness was in the middle of the second decade of life. The muscle atrophy was more severe in the female members. Electromyographic examination of the atrophic muscles showed evidence denervation. One female patient demonstrated slow motor conduction velocity in the right median nerve.     

Neurologic complications in a case of Werner syndrome

A 39 year old caucasian man was admitted in 1994 to the neurological department with a left pure motor hemiplegia that appeared suddenly. This patient showed typical features of Werner's syndrome. He had a hoarse voice, a diffuse muscle weakness and atrophy in the upper and lower limbs with chronic ulcers on the legs. His scalp and public hair were sparse. Cranial MRI revealed several lesions in the white matter, low signal intensity on T1 weighted images and high signal on T2 weighted images. Cerebrospinal fluid (CSF was inflammatory with hypercytosis and proteinorachia was 0.50 g/l with synthesis of IgG. Sural nerve biopsy revealed muscle atrophy and the loss of myelinated fibers. Thus, central and peripheral nervous systems were affected in this case.     

Glycogenolysis stimulation by non-steroidal anti-inflammatories in the perfused rat liver is not accompanied by Ca2+ release

To better understand the characteristics of amyloid deposition in the choroid plexus, we examined autopsied brain by routine histology, immunohistochemistry, and electron microscopy in three group of patients: primary systemic amyloidosis (n = 7), cerebral amyloid angiopathy (CAA, n = 6), and controls (n = 3). Three of the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid deposits of the choroid plexus were seen in six of the seven cases of systemic light chain amyloidosis. Immunohistochemistry revealed that the deposited amyloids had reactivity for immunoglobulin light chain and amyloid P component. Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils along the epithelial basement membrane as well as in the vascular walls was ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits were consistently present in meningeal blood vessels and were often found in senile plaques of the cerebral parenchyma; congophilic amyloid deposits were absent in the choroid plexus. Choroid plexus epithelial cells exhibited immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C-terminal-specific antibodies; in particular, consistent staining was obtained for the latter antibody. Immunoreactivity for amyloid beta protein (A beta) with monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial cells. These findings suggest that amyloid deposition of the choroid plexus depends on the major component protein in amyloidosis, and that the choroid plexus may produce APP and A beta protein although A beta amyloidosis is not evident in the choroid plexus.     

Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.     

Axonal neuropathy and predominance of type II myofibers in infantile spinal muscular atrophy

Two affected siblings with infantile spinal muscular atrophy (SMA I) presented with generalized muscular hypotonia, which progressed to early death. Quadriceps muscle biopsy did not show the typical neurogenic pattern of spinal muscular atrophy. The histochemical fiber type determination revealed a predominance of type II fibers without type I hypertrophy, an unprecedented finding in spinal muscular atrophy. Sural nerve biopsy exhibited findings typical for axonal neuropathy. In one patient, electrical stimulation of peripheral nerves showed an inexcitability of motor and sensory nerves. Genetic studies revealed homozygous deletions of the telomeric survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene in the affected children. This is the second case report of molecular genetically proven spinal muscular atrophy associated with axonal neuropathy. We conclude atypical findings on muscle biopsy and evidence of axonal neuropathy are compatible with the diagnosis of infantile spinal muscular atrophy.     

A case of hereditary motor and sensory neuropathy type I with a new type of peripheral myelin protein (PMP)-22 mutation

A 16-year-old school boy suffered from an insidious foot deformity. Slight degrees of symmetrical muscular weakness of the distal lower limb muscles were observed. In addition, slight degrees of atrophy of the anterior tibial muscles with moderate degrees of pes cavus deformity and flexion contracture of the toes of both feet were observed. In the upper and lower limbs muscle stretch reflexes were decreased and absent, respectively. Vibratory and touch sensations were moderately and slightly decreased, respectively, in the toes. The median and ulnar motor conduction velocities (m/sec) were 21.1 and 13.2, respectively, with markedly prolonged distal latencies. The median and ulnar sensory conduction velocities (m/sec) were 21.5 and 10.1, respectively. No M-waves were recorded by stimulation of the tibial and peroneal nerves. Also no nerve action potential was elicited by stimulation of the sural nerve. A fascicular biopsy of the sural nerve was performed. The myelinated fibers showing segmental de- and re-myelination were frequently found in teased fiber preparations. The density of myelinated fibers was markedly decreased, and both demyelinated axons and onion-bulbs were also observed by light and electron microscopy in the Epon-embedded sections. Based on the neurological examination and nerve conduction studies, although other family members were not examined, a diagnosis of HMSN type I was made. To clarify the genetic abnormality, a systematic study of the genomic DNA was made. A DNA duplication in the chromosome 17p11.2-12 was not observed. The single-strand conformational polymorphism method showed an abnormal extra band in the exon 3 encoding peripheral myelin protein (PMP)-22 gene of the patient compared with the control. The direct sequencing analysis of the exon 3 revealed a guanine to cytosine substitution that caused a substitution of arginine for glycine at amino acid position 93 of PMP-22. The digestion of the exon 3 with Sty I showed the presence of a mutant and normal allele of the PMP-22 gene indicating autosomal dominant heredity. This type of PMP-22 gene mutation is different from any type of PMP-22 mutations reported in the literature. The mutation is located in the intracellular domain of PMP-22. The mechanism by which the mutation induce demyelination of the peripheral myelin remains to be elucidated. Reports of patients with a point mutation of amino acids of PMP-22 are rare in the literature. This is the first Japanese patient with a new type of mutation of the PMP-22 gene.     

The sword of Damocles: the psychosocial impact of familial spinocerebellar ataxia in South Africa

It has been recently recognized that increased titers of serum anti-GM1 antibodies may be associated with motoneurone diseases or with multiple motor neuropathy with or without conduction block and also with chronic sensorimotor neuropathy and Guillain-Barré syndrome. Santoro et al. were the first to note that anti-GM1 antibodies were able to bind to the nodes of Ranvier of the sural nerve of a patient with clinical signs and symptoms mostly resembling amyotrophic lateral sclerosis who also showed, in nerve conduction studies, multifocal motor nerve fibers conduction block and serum IGM anti-GM1 antibodies. The two patients presented in this report had asymetrical motor neurone disease with signs and symptoms of lower motoneurone involvement, and other signs, in the first patient, which suggested the existence of upper motoneurone damage. Besides, the second patient also had clinical sensory impairment in the lower limbs. Electrophysiologically, none of them had nerve conduction block but both showed inexcitable median and sural nerve sensory fibers. Both had high titers of anti-GM1. A sural biopsy of both patients showed immunoglobulins into the sensory fibers. However, we do not know whether the anti-GM1 antibodies bind to a cross-reactive glycolipid other than the GM1 itself. In any case, it seems that the presence of anti-GM1 antibodies might be a marker signalling a potentially treatable immune disorder which may have signs of lower and upper motor neurone disease and, also, clinical and electrophysiological evidences of peripheral sensory involvement.     

Cardiac dysfunction in female gene carriers of Duchenne muscular dystrophy

Cardiac dysfunction and its correlation with skeletal muscle dysfunction were examined in 16 definite female gene carriers of Duchenne muscular dystrophy (DMD). Five out of 16 carriers (31.3%) had cardiac symptoms and 8 carriers (50.0%) showed an increased cardio-thoracic ratio on chest X-ray. Electrocardiographic abnormalities including a high R:S ratio (> or = 1.0) in the V1 lead, deep Q wave (> 3 mm) in the I, II, aVL, V5, and V6 leads, complete right bundle branch block and premature ventricular beats, were observed in 9 carriers (56.3%). On echocardiographic examination, an increase in the end-diastolic dimension of the left ventricle and a decrease in the ejection fraction suggestive of dilated cardiomyopathy were found in 12 carriers (75.0%). Tl-201 myocardial SPECT scan was performed in 2 symptomatic carriers and showed an area of hypoperfusion in the inferio-posterior wall. These findings were similar to previously reported findings in DMD patients. A biopsy of the myocardium was obtained in one carrier with her informed consent for the biopsy. Immunohistochemical staining demonstrated that 75.4% of the myocardial fibers were negative for dystrophin, suggesting that her cardiac dysfunction is caused by the abnormal expression of dystrophin in the cardiac muscle. On examination of the skeletal muscle function, none of the carriers had clinical evidence of muscle weakness or atrophy. However serum creatine kinase activity was elevated in 14 of 16 carriers (87.5%). Computed tomography (CT) of the lower limb muscles demonstrated widened spaces among muscles and moss-eaten appearance of low density areas within muscles and CT value was decreased, suggesting the subclinical involvement of the skeletal muscle. In the carriers without cardiac symptoms, there was a negative correlation (p < 0.05) between the end-diastolic dimension of the left ventricle and the CT value of the biceps femoris muscle (a muscle with the lowest CT value among the lower limb muscles). This indicates that there was an apparent correlation between the cardiac and skeletal muscle dysfunction. These findings suggest a high frequency of clinical and subclinical involvement of the cardiac and skeletal muscles in DMD carriers. To protect them from cardiac failure, cardiac dysfunction in DMD carriers needs to be examined closely and treated appropriately before the carriers become symptomatic.     

Functional differentiation of human naive helper T cells

Here we report a case of a 56-year-old male with post-poliomyelitis muscular atrophy (PPMA), who presented with cranial nerve signs and widespread atrophy of the extremities. He had suffered from poliomyelitis at the age of 2 years. After recovery from the acute stage, the paralysis remained in his left arm. He noticed muscle weakness of the right upper and lower extremities at the age of 45 years and the muscle atrophy progressed to his arms, hip and thigh at the age of 55 years. Neurological examination revealed muscle atrophy of the neck and disturbance of left V, VIII, IX, X and bilateral XI cranial nerves. We diagnosed this case as PPMA from his history and electromyographic and muscle biopsy findings which suggested chronic denervation. Among the 21 PPMA cases in the past in which the acute poliomyelitis had resulted in paralysis of the only one limb, ours was the only case that had muscle atrophy of all the limbs. Cranial nerve involvement is known to occur in acute poliomyelitis; therefore, there is a possibility that the involvement of the cranial nerves in our case might be a delayed progressive symptoms.