Distal myasthenia gravis: case report

We report the case of a 30-year-old woman with a 7-year history of distal lower limbs weakness that evolved to upper limbs weakness. On neurological examination, she presented normal cranial nerves, bilateral quadriceps and feet interosseous atrophy, normal muscular tonus, muscular weakness more severe in dorsal feet interosseous and anterior tibial, and decreased deep tendon reflexes. Repetitive nerve stimulation of the ulnar and fibular nerves showed a decrement greater than 10% of the compound muscle action potential. Antibody against acetylcholine receptor titer was positive. Computed tomography scan of the thorax was normal. Thyroid function tests showed evidence of hyperthyroidism. Distal muscular weakness is a rare onset presentation of myasthenia gravis. However, myasthenia gravis must be considered in the differential diagnosis of distal limb weakness.     

Symptoms of activity-induced weakness in peripheral nervous system disorders

Activity-induced weakness was reported in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). This was attributed to activity-dependent conduction block (CB) arising in demyelinated axons. It is not known if activity-induced weakness is common, nor if it is specific for MMN and CIDP. We, therefore, carried out an investigation by questionnaire in 64 MMN patients, 52 CIDP patients, 48 progressive spinal muscular atrophy (PSMA) patients, and 30 normal subjects. Subjects were asked if they experienced an increase in weakness when performing 10 common tasks. The percentage of tasks causing activity-induced weakness was higher in the patient groups than in the normal subjects (p < 0.001). The risk of activity-induced weakness exceeding that in normal subjects was sixfold higher for each patient group when adjusted for sex, age, and a fatigue score. With further adjustment for scores of weakness and axon loss, no significant differences were found between the patient groups. In conclusion, activity-induced weakness is frequently reported in MMN and CIDP. It is, however, not specific for these neuropathies as PSMA patients reported it to the same extent.     

Single fiber electromyography in myasthenia gravis during pregnancy

We report the use of single fiber electromyography (SFEMG) to demonstrate changes in the physiologic abnormality of myasthenia gravis (MG) during pregnancy. A 23-year-old became pregnant 15 months after the onset of mild ocular weakness. On initial evaluation, SFEMG jitter measurements demonstrated a slight abnormality of neuromuscular transmission. There was no change in severity of clinical disease or jitter measurements until the third trimester, when she improved. Jitter measurements at that time were normal. Labor was normal and she delivered a normal male. Three days postpartum, myasthenic weakness recurred temporarily and jitter measurements showed worsening. At 16 days and 6 weeks postpartum, she had only minimal medial rectus weakness and jitter studies were normal. Three months postpartum, ocular symptoms recurred and jitter measurements were slightly abnormal. She continued to worsen, developing limb muscle and severe ocular muscle weakness at 4 months postpartum. She was treated with plasma exchange and thymectomy. Prednisone was added 2 months after thymectomy due to continued worsening and development of oropharyngeal weakness. Three years postpartum she was taking prednisone 10 mg every other day and had only slight weakness of neck flexors, and jitter studies were again normal. © 1993 John Wiley & Soncs, Inc.     

Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations

Summary The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.     

Dynamic properties of partially denervated muscle in children with brachial plexus birth palsy.

Contraction time, time to peak rate of tension development, half-relaxation time and maximum twitch tension of partially denervated flexor carpi ulnaris muscle were measured in children with brachial plexus birth palsy. The extent of weakness of the affected muscle was assessed by expressing its maximum twitch tension as a percentage of the tension of the contralateral normal muscle. Contraction time, time to peak rate and half-relaxation time were prolonged in children with severe weakness, while in children with moderate weakness only half-relaxation time was prolonged. The contralateral normal flexor carpi ulnaris muscle showed age differences in its contractile properties, while in the affected muscle such differences were not found. This result suggests that denervation at birth impairs normal development of muscle contractile properties.     

Diagnostic value of Hoover sign and motor-evoked potentials in acute somatoform unilateral weakness and sensory impairment mimicking vascular stroke

Acute unilateral weakness along with sensory impairment is commonly caused by obstruction of major cortical arteries in either adults or children. A somatoform presentation mimicking acute vascular stroke is very rare, especially in the pediatric age group. Here we report three adolescents presenting with acute unilateral weakness and sensory impairment along with diminished tendon reflexes who were suspected to have an acute stroke but who had developed a somatoform psychogenic disorder. Two adolescents had complete hemiplegia and one had weakness of the left leg - two had moved the alleged paralytic limbs during sleep. A normal Hoover sign was suggestive of a somatoform psychogenic etiology rather than true vascular stroke. Cortical and spinal MRI, motor-evoked potentials (MEP) and somatosensory-evoked potentials were normal. All adolescents recovered completely. Therefore, a somatoform conversion reaction should be considered in children presenting with acute unilateral weakness and sensory alterations, which is corroborated by a normal Hoover sign and intact MEP.     

Adynamia episodica hereditaria: What causes the weakness?

The cause of weakness was investigated in a patient with adynamia episodica hereditaria without myotonia. A pattern of exercise and rest produced episodes of hyperkalemic periodic paralysis. In addition, local muscle weakness was induced by forearm cooling. Investigations on isolated intercostal muscle demonstrated that a high potassium concentration in the bathing solution triggered a noninactivating membrane current causing depolarization of the muscle fibers. This current was carried by sodium as it could be inhibited by tetrodotoxin. The abnormal sodium conductance led to an increase of sodium within the fibers. This was demonstrated directly by intracellular recordings. Weakness induced by rest after exercise and cold-induced weakness appeared to have different pathomechanisms. In the cold, the muscle fibers retained a normal resting potential, but their excitability was reduced and their mechanical threshold was increased. These findings also provide evidence that the mechanism of cold-induced weakness in adynamia episodica is distinctly different from the cold-induced weakness that occurs in paramyotonia congenita.     

A case of myasthenia gravis complicated by cyclic thrombocytopenia]

A 47-year-old woman with myasthenia gravis for last 11 years was admitted because of relapsed muscle weakness, hypermenorrhea and thrombocytopenia. Physical and neurological examinations revealed diplopia, proximal muscle weakness and purpuras on the left arm and bilateral legs. Repeated hematological examinations revealed cyclic fluctuation of platelet counts which spontaneously changed from the nadir levels of 12-27 x 10(3)/microliters to the peak levels of 150-400 x 10(3)/microliters. The platelet count reached a nadir at the onset of menstruation. Platelet-associated IgG (PAIgG) was within normal level when platelet count was at an increasing phase. Survival time of autologous platelets was normal when platelet count was at an increasing phase. Megakaryocytes in the bone marrow were apparently normal at the nadir phase. The patient's serum obtained at the nadir of platelet count significantly suppressed megakaryocyte colony forming unit (Meg-CFU) formation in comparison with that after the stabilization of platelet count, suggesting that this cyclic thrombocytopenia was secondary to cyclic hypoproduction of megakaryocytes caused by a suppressive factor. On the other hand muscle weakness showed no cyclic fluctuation. Administration of 60 mg/day prednisolone stabilized the platelet count at about 280 x 10(3)/microliters, abolished hypermenorrhea and gradually improved muscle weakness. These findings suggested autoimmune mechanism in the production of a Meg-CFU-suppressive factor might be involved in the pathogenesis of thrombocytopenia.     

Adult phosphorylase b kinase deficiency

Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.     

Potentially fatal cardiac dysrhythmia and hyperkalemic periodic paralysis

An 11-year-old boy was evaluated for mild periodic muscular weakness exacerbated on separate occasions by disopyramide phosphate and procainamide. He and his mother both had bidirectional ventricular tachydysrhythmia (BVT), short stature, microcephaly, and clinodactyly. The mother, but not the child, had lingual myotonia. The two antiarrhythmic drugs worsened the muscular weakness without benefiting the cardiac dysrhythmia. Potassium loading produced skeletal muscle weakness and transient conversion of the BVT to normal sinus rhythm. Hypokalemia aggravated the BVT without causing weakness. Acetazolamide had no effect. The patient suffered a nonfatal cardiac arrest after several days of increased carbohydrate intake. Imipramine controlled the dysrhythmia without inducing weakness. Periodic paralysis should be considered as the diagnosis in children with BVT, a potentially fatal condition.     

Median nerve somatosensory evoked potentials and their high-frequency oscillations in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate sensory cortical changes in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) and their high-frequency oscillation potentials. METHODS: Subjects were 15 healthy volunteers and 26 ALS patients. Median nerve SEPs were recorded and several peaks of oscillations were obtained by digitally filtering raw SEPs. The patients were sorted into three groups according to the level of weakness of abductor pollicis brevis muscle (APB): mild, moderate and severe. The latencies and amplitudes of main and oscillation components of SEP were compared among normal subjects and the three patient groups. RESULTS: The early cortical response was enlarged in the moderate weakness group, while it was attenuated in the severe weakness group. No differences were noted in the size ratios of oscillations to the main SEP component between the patients and normal subjects. The central sensory conduction time (CCT) and N20 duration were prolonged in spite of normal other latencies. CONCLUSIONS: The median nerve SEP amplitude changes are associated with motor disturbances in ALS. The cortical potential enhancement of SEPs with moderate weakness in ALS may reflect some compensatory function of the sensory cortex for motor disturbances. SIGNIFICANCE: The sensory cortical compensation for motor disturbances is shown in ALS, which must be important information for rehabilitation.     

Rapidly evolving myopathy with myosin-deficient muscle fibers

Five patients with rapidly evolving, severe weakness had an unusual myopathy with virtually complete loss of myosin in 5 to 40% of muscle fibers. Three of the 5 patients began to develop weakness 1 to 2 weeks after lung transplantation. The fourth became weak after a febrile illness. The fifth presented with diabetic ketoacidosis and weakness. All patients had received corticosteroid therapy. In all cases the weakness was progressive and led to severe disability, with respiratory failure in 4 patients. Initial diagnostic testing did not localize an underlying cause for the weakness. Creatine kinase was normal or minimally elevated. Electromyography generally showed mildly myopathic or nondiagnostic changes. However, muscle biopsy revealed numerous small angular fibers with no myosin ATPase staining at any pH. Immunocytochemical staining and ultrastructural studies confirmed a severe loss of myosin in many fibers. This rapidly evolving myopathy with myosin-deficient muscle fibers appears to be different clinically and pathologically from previously described syndromes involving rapidly progressive weakness. Slow recovery over a period of months is the most common outcome.     

An unusual case of neonatal myasthenia

An unusual case of neonatal myasthenia gravis is reported in an infant who had respiratory failure due to diaphragmatic weakness. Although power and tone in the limbs were normal, fatiguability of both diaphragm and peripheral muscles was demonstrated. Acetylcholine receptor antibodies were absent in the mother, which suggests that an alternative humoral mechanism may have been responsible for the transient (6-week) neonatal weakness.     

A family with oculopharyngeal muscular dystrophy with (GCG)9 expansion in which a sister had neck as well as proximal and her brother proximal lower limb muscle weakness]

We report a 58-year-old woman (patient 1) and her 60-year-old brother (patient 2) with autosomal dominant oculopharyngeal muscular dystrophy. Patient 1 first noticed blepharoptosis and neck weakness at age 55. On neurological examination, she showed bilateral blepharoptosis and weakness in the neck and upper proximal limbs. Serum creatine kinase (CK) level was slightly elevated. Her older brother first noticed blepharoptosis and lower limb weakness at age 51. On neurological examination, he showed bilateral blepharoptosis, slight ophthalmoparesis and bilateral iliopsoas muscle weakness. Serum CK level was normal. Esophageal fluoroscopy disclosed dysfunction of the constrictor pharyngeal muscles. Muscle biopsy of them showed myopathic changes with rimmed vacuoles. The (GCG)9 mutation in the poly (A) binding protein 2 gene was identified, which was the same as seen in the large French-Canadian kindred in Quebec in Canada. The clinical phenotype in patient 2 is similar to that of French-Canadian patients but it in patient 1 is different in distribution of muscle weakness.     

Neonatal ophthalmoplegia with microfibers: a reversible myopathy?

An infant born with marked hypotonia showed prompt regression of skeletal muscle weakness, but by 7 weeks of age had total external ophthalmoplegia. Biopsy of the gluteus muscle at 14 days showed marked variation in fiber size with a large proportion of very small fibers (less than 3 mu). By 10 months of age, biopsy of the vastus was virtually normal. The inferior oblique muscle was replaced by fibrous tissue containing a few remaining degenerating fibers. The child was normal at 2 years of age except for mild facial weakness and ophthalmoplegia. This syndrome may be the result of a reversible intrauterine process.     

Hoover's sign for the diagnosis of functional weakness: A prospective unblinded cohort study in patients with suspected stroke

ObjectiveHoover's sign – weakness of voluntary hip extension with normal involuntary hip extension during contralateral hip flexion against resistance – is a commonly used sign in the diagnosis of functional weakness of the lower limb. However, little is known about the performance of this sign in clinical practice.MethodsHoover's sign was tested as part of the diagnostic work-up of 337 patients presenting to hospital with suspected stroke. We made a gold-standard diagnosis of stroke, functional disorder, or other diagnosis based on clinical history and examination, imaging and clinical follow-up. We calculated the sensitivity, specificity, positive and negative predictive values of Hoover's sign for a diagnosis of functional weakness in patients who presented with leg weakness.ResultsWe consecutively recruited 337 consecutive patients with suspected stroke, 124 of whom presented with leg weakness. 8 of these patients had a diagnosis of functional disorder. The sensitivity of Hoover's sign for a diagnosis of functional weakness in those who presented with leg weakness was 63% (95% CI: 24 to 91), and the specificity was 100% (95% CI: 97 to 100).ConclusionsIn this cohort, Hoover's sign was moderately sensitive and very specific for a diagnosis of functional weakness. Further studies are required to assess inter-observer variability and performance of the test in larger numbers of patients with functional weakness.     

A case of Hopkins syndrome with onset at puberty]

The patient was a 15-year-old man who developed weakness of left leg 6 days after an acute asthmatic attack. Neurological examination revealed severe muscle weakness and atrophy at L5-S1 level and mild muscle weakness and atrophy at L2-4 level in the left leg. Deep tendon reflexes were normal in the upper limbs and slightly brisk in the lower limbs except for absence of Achilles tendon reflex on the left. His sensation was normal. Needle EMG revealed neurogenic changes in both the left (L2-S1) and right (L2-4) leg muscles. Motor nerve conduction study of the left tibial and peroneal nerves revealed a marked reduction of amplitude and mild reduction of MCV. F-wave was not evoked in either nerves. Sensory nerve conduction study of the left sural nerve was normal. The titers of anti-viral antibodies in the paired sera showed no significant changes in any viruses examined including echovirus, enterovirus, coxsackievirus and poliovirus type 1, 2 and 3. The serum IgE was elevated (1,300 IU/ml) and mite antigen-specific IgE was strongly positive. Spinal cord MRI revealed no abnormality in either thoracic or lumbar spinal cord. This patient was diagnosed as a rare case of Hopkins syndrome with onset at puberty.     

CT-scanning of skeletal muscle in arthrogryposis multiplex congenita

CT-scanning of skeletal muscles was performed on 14 patients with arthrogryposis multiplex congenita (AMC), according to an eight-slice protocol. Adipose tissue replacement and atrophy of muscles was found in six patients with neurogenic or myopathic origin of AMC, associated with severe muscle weakness. In the remaining patients with other forms of AMC, in which muscle weakness was less marked or absent, muscular CT-scanning was normal. It is stated that muscular CT-scanning is not a routine investigation in a screening procedure of all cases of AMC. However, CT-scanning appears to be useful in cases of severe AMC with associated muscle weakness in detecting the neurogenic and myopathic forms. It also facilitates the selection of a suitable site for EMG and biopsy and may provide important information for orthopaedic management.     

Limb-girdle myasthenia gravis in a 10-year-old girl: a case report

A 10-year-old girl presented with progressive proximal limb muscle weakness without facial, ocular, or bulbar muscle involvement. There was no fatigability or diurnal fluctuation in symptoms. Her weakness worsened with febrile illnesses and recovered with accruing disabilities over a few weeks. Serum creatine kinase levels and muscle biopsy were normal. A significant decrement on repetitive nerve stimulation test and positive response to therapeutic neostigmine challenge test confirmed the diagnosis of limb-girdle myasthenia. She responded well to corticosteroids and thymectomy, demonstrating a likely autoimmune etiology. This case highlights the long-term fluctuations in a case of myasthenia gravis and the need for a high index of suspicion for myasthenia in children presenting with unexplained muscle weakness, even in the absence of typical features such as fatigability, diurnal fluctuation, and oculobulbar weakness.     

A mitochondrial myopathy in an infant with lactic acidosis

We describe a girl with mitochondrial myopathy, who presented with general muscle weakness, muscle hypotonia and motor retardation. The level of blood lactate and pyruvate was consistently increased. Enzymatic studies showed impairment of NADH-dehydrogenase activity (complex I of the respiratory chain) in skeletal muscle. Electron-microscopy of a muscle biopsy showed abnormalities of a mitochondrial myopathy. The girl, now aged 30 months, has been treated with riboflavine (vitamin B2) since the age of 14 months, and lactate and pyruvate levels have decreased to normal. The patient still shows mild muscle hypotonia and weakness, but good motor progress and normal cognitive development.