Congenital myasthenic syndrome associated with paucity of synaptic vesicles and reduced quantal release.
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Acetylcholine↗
Biomedical subjects
C M Harper
Publications and source records attributed to C M Harper.
The spectrum of congenital end-plate acetylcholinesterase deficiency.
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Acetylcholinesterase↗
Congenital end-plate acetylcholine receptor deficiency and short channel open time.
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Child, Preschool↗
Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel.
We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.
Adult↗
Congenital myasthenic syndromes: I. Deficiency and short open-time of the acetylcholine receptor.
A 5.5-year-old girl had myasthenic symptoms since birth. Tests for antiacetylcholine receptor (AChR) antibodies were negative. To investigate the character of the neuromuscular transmission defect, an intercostal muscle specimen was obtained at age 27 months. Immune deposits were absent from the endplates. On electron microscopy, most postsynaptic regions appeared normal, but the density of AChR on the junctional folds was diffusely reduced. In vitro microelectrode studies revealed that the number of transmitter quanta released by nerve impulse was normal. The amplitude of miniature of endplate potentials and currents was abnormally low. A study of the kinetic properties of AChR by analysis of acetylcholine-induced current noise demonstrated a significant decrease in mean channel open-time; the mean channel conductance was normal. The safety margin of neuromuscular transmission in this disorder is likely to be compromised by the deficiency and abnormal kinetic properties of AChR. The findings are unique among those patients with congenital AChR deficiency described to date.
Acetylcholinesterase↗
Thymoma.
Thymomas and thymic carcinomas are thymic epithelial tumors that constitute approximately 15% of all mediastinal masses. From 28 to 66% of thymomas cause chest symptoms as the initial manifestation; the rest are discovered on routine chest roentgenograms or during investigations prompted by the presence of a paraneoplastic syndrome. Forty percent of patients with thymoma have one or more paraneoplastic syndromes, including myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. Extrathymic malignant lesions develop in up to 20% of patients. Traditional histologic classifications have not accurately predicted tumor behavior; a recently developed classification based on cellular differentiation toward thymic medullary or cortical epithelium may correlate better with prognosis. Nevertheless, the prognosis is best predicted by stage of the tumor determined intraoperatively and is poorer in patients with incomplete resection than in those with complete resection of the thymoma. In addition to surgical intervention, irradiation and chemotherapy have important roles in the management of thymomas, particularly in advanced stages. In this article, the clinical manifestations, diagnosis, pathologic features, staging, and treatment of thymomas are reviewed, and the prognosis of affected patients is discussed.
Humans↗
Congenital endplate acetylcholinesterase deficiency.
Endplate acetylcholinesterase (AChE) consists of globular catalytic subunits attached to the basal lamina by a collagen-like tail. Different genes encode the catalytic subunit and the tail portion of the enzyme. Endplate AChE deficiency was reported previously in a single case (Engel et al., 1977, patient 1). We describe here our observations in four additional patients (patients 2-5). Three cases were sporadic; patients 2 and 3 were sisters. All had generalized weakness increased by exertion but ophthalmoparesis was not a constant feature. All had mild slowing of the pupillary light reflex; other dysautonomic features were absent. None benefited from anticholinesterase therapy. All patients had a decremental electromyogram response; in four of the five patients, single nerve stimuli evoked a repetitive response. Miniature endplate potential amplitude was reduced in patient 5 only. Endplate amplitudes and currents were prolonged but the open-time of the acetylcholine receptor ion channel was normal. In patients 1-4 the quantal content of the endplate potential was reduced due to a reduced number of readily releasable quanta. Quantitative electron microscopy revealed abnormally small nerve terminals, abnormal encasement of the presynaptic membrane by Schwann cells and degeneration of junctional folds and of organelles in the junctional sarcoplasm. Acetylcholinesterase was absent from all endplates of all patients by cytochemical and immunocytochemical criteria. Density gradient ultracentrifugation of muscle extracts from patients 1, 3, 4 and 5 revealed an absence of the collagen-tailed form of the enzyme in patients 1, 3 and 4 but not in patient 5. The kinetic properties of the residual AChE in muscle were normal. Erythrocyte AChE activity and Km values, determined in three patients, were also normal. Studies of the catalytic subunit gene of AChE in patients 2 and 3 revealed no abnormality in those exons that encode the domain to which the tail subunit binds. In patients 1-4 the molecular defect is likely to reside in the gene encoding the tail subunit of AChE, or in a protein necessary to assemble the catalytic and tail subunits. In patient 5, the absence of AChE from the endplate may be due to a faulty tail subunit, a defect in the basal lamina site that binds the tail subunit or failure of transport of the assembled asymmetric enzyme from the cell interior to the basal lamina. The cause of the weakness in these patients is not fully understood but possible mechanisms are discussed.
Acetylcholinesterase↗
Intraoperative electrophysiological monitoring in children.
Children, like adults, are at risk for neurological injury during a variety of surgical procedures. Intraoperative electrophysiological monitoring (IOM) provides information about the functional integrity of the nervous system during surgery. This information may determine the mechanism of injury and prevent damage by identifying nerves and detecting dysfunction at a reversible stage. Electrophysiological techniques may also help direct therapy by improving injury localization, detect the presence or absence of axonal integrity in peripheral nerve lesions, and identify rootlets with the greatest contribution to spasticity in patients undergoing selective dorsal rhizotomy (SDR). Electrophysiological techniques used are modified from those employed in the diagnostic laboratory. The first portion of this article reviews IOM experience at the Mayo Clinic in patients under 18 years of age from 1985 to 1991. The types of procedures monitored, the monitoring modalities used, technical problems unique to children, and neurological outcome are discussed. Subsequently presented are the application and techniques of electrophysiological monitoring during SDR as currently practiced at the University of Kentucky and other medical centers.
Brain Stem↗
Effect of BAEP monitoring on hearing preservation during acoustic neuroma resection.
We measured the effect of brainstem auditory evoked potential (BAEP) monitoring on hearing preservation in acoustic neuroma resection in 90 consecutive patients with monitoring compared with 90 historical controls matched for tumor size and preoperative hearing status. In small tumors (less than 2 cm), BAEP monitoring was associated with a higher rate of hearing preservation and a greater chance that the hearing preserved was clinically useful. Changes in the BAEP intraoperatively showed a good correlation with postoperative hearing status.
Evoked Potentials, Auditory, Brain Stem↗
Current results of the retrosigmoid approach to acoustic neurinoma.
Since 1984 when cranial nerve monitoring became routinely performed at the Mayo Clinic, 255 patients have undergone 256 procedures using the retrosigmoid approach for the removal of acoustic neurinomas. Of these, 221 patients had some hearing before surgery and 52 maintained hearing following surgery. The anatomical continuity of the facial nerve was preserved in 237 of these 256 procedures. It was possible to perform a primary end-to-end anastomosis in seven of the remaining 19 patients, and one patient had a cable graft inserted. Thus, 95.7% of these patients were believed to have potential for spontaneous facial nerve function. Of the 11 patients in whom this was not possible, seven underwent early spinal accessory facial anastomosis, in two hypoglossal-facial anastomosis was performed, and two had no facial nerve procedures and have paralysis of the facial nerve. There were two deaths from a pulmonary embolus in the early postoperative period, both 4 days following otherwise uneventful surgery. The most common postoperative complication was cerebrospinal fluid leakage, which has not resulted in significant permanent morbidity although early repair for this problem is now routinely recommended. Other complications were quite rare and have generally not resulted in any major change in patient lifestyle or activity level. This review reconfirms that the retrosigmoid surgical treatment of acoustic tumors continues to be an acceptable treatment option.
Adolescent↗
Spinal cord injury in experimental thoracic aortic occlusion: investigation of combined methods of protection.
The efficacy of combined methods of spinal cord protection during thoracoabdominal aortic reconstruction was evaluated because a recent clinical study failed to substantiate the value of cerebrospinal fluid drainage when used alone in the prevention of paraplegia. The effect of cerebrospinal fluid drainage and aortofemoral shunting were analyzed with regard to neurologic outcome and spinal cord blood flow in a model of thoracic aortic occlusion. In addition, we studied the use of motor-evoked potentials as compared with somatosensory-evoked potentials in monitoring cord perfusion. Thirty-two dogs underwent proximal and distal thoracic aortic occlusion for 60 minutes. The control group (n = 8) underwent thoracic aortic cross-clamping only. Spinal cord protection was used in three groups: cerebrospinal fluid drainage alone (n = 8), aortofemoral shunting alone (n = 8), and cerebrospinal fluid drainage and aortofemoral shunting (n = 8). Neurologic outcome improved in all treatment groups as compared with controls (p less than 0.001). The addition of cerebrospinal fluid drainage to aortofemoral shunting did not further improve neurologic outcome. Spinal cord blood flow measured with microspheres in the lumbar gray matter was significantly higher in the dogs with aortofemoral shunting (+/- cerebrospinal fluid drainage) as compared with those with cerebrospinal fluid drainage alone (p less than 0.05) or the controls (p less than 0.001). Aortofemoral shunting also prevented the development of acidosis and hyperglycemia. Loss or changes in amplitude and latency of motor-evoked potentials did not distinguish between the groups. Loss of somatosensory-evoked potentials had a high sensitivity (92%) but lower specificity (68%) in predicting neurologic injury, whereas loss of motor-evoked potentials had a high specificity (100%) but a very low sensitivity (16%). We conclude that cerebrospinal fluid drainage or aortofemoral shunting significantly improve spinal cord blood flow and neurologic outcome. The greatest increase in spinal cord blood flow was seen with aortofemoral shunting, which also prevented metabolic disturbances of reperfusion. Although the addition of cerebrospinal fluid drainage to aortofemoral shunting was the only group in which no neurologic injury occurred, this group did not have a significant improvement in outcome when compared with aortofemoral shunting alone. Spinal cord ischemia was more accurately detected with somatosensory-evoked potentials when aortofemoral shunting was used, whereas motor-evoked potentials recorded from the spinal cord were not sensitive enough to predict neurologic injury.
Analysis of Variance↗
Auditory monitoring during acoustic neuroma removal.
Preservation of hearing has become attainable for patients with small acoustic neuromas. Brain-stem auditory evoked response was monitored intraoperatively in 60 patients undergoing acoustic neuroma surgery via the posterior fossa approach. The overall rate of hearing preservation was 30% in the monitored group and 20% in 60 patients who were matched for tumor size and preoperative hearing level and underwent the same surgical procedure but without intraoperative brain-stem auditory evoked response monitoring. The rate of hearing preservation was correlated with tumor size: with tumors less than or equal to 1 cm, hearing was preserved in 82% of monitored and 36% of unmonitored patients; hearing was not preserved with tumors larger than 3 cm. Intraoperative brain-stem auditory evoked response monitoring appears to have improved the preservation of hearing during removal of small tumors.
Adolescent↗
AAEM case report #21: hemifacial spasm: preoperative diagnosis and intraoperative management.
A 75-year-old man developed progressive involuntary hemifacial spasm. Electrophysiologic evidence of abnormal cross-transmission between neurons of the facial nerve was demonstrated. Electrodiagnostic studies were used to confirm the diagnosis preoperatively and determine the adequacy of vascular decompression of the facial nerve intraoperatively.
Aged↗
Paraneoplastic brachial plexopathy in a patient with Hodgkin's disease.
We describe a case of inflammatory brachial plexopathy that occurred in the context of a mild, diffuse sensorimotor peripheral neuropathy associated with Hodgkin's disease. Clinical, electrophysiologic, and pathologic studies helped distinguish this disorder from other causes of brachial plexopathy in patients with cancer. Treatment with corticosteroids seemed beneficial in this patient. We suggest that this may be another type of paraneoplastic condition associated with Hodgkin's disease.
Adult↗
Failure of motor evoked potentials to predict neurologic outcome in experimental thoracic aortic occlusion.
Motor evoked potential monitoring was tested as an alternative to somatosensory evoked potential monitoring in evaluating spinal cord function during thoracic aortic occlusion in dogs. Twenty-seven animals underwent 60 minutes of cross-clamping of the proximal descending thoracic aorta with (n = 18) or without (n = 9) cerebrospinal fluid drainage. Spinal cord blood flow was measured with microspheres, and neurologic outcome was evaluated at 24 hours with Tarlov's scoring system. Cerebrospinal fluid drainage improved neurologic outcome (p less than 0.05). Motor evoked potentials recorded over the lumbar spinal cord were lost in 9 of 20 dogs with ischemic cord injury and were not lost in any of the 7 dogs that were neurologically normal. Somatosensory evoked potential were lost in 19 of 20 paraplegic/paraparetic dogs and lost in 3 of 7 normal dogs (p less than 0.01). After reperfusion, motor evoked potentials returned in all nine neurologically injured dogs that lost the potentials and were still present at 24 hours. Changes in amplitude, latency, or time until loss or return of motor evoked potentials or somatosensory evoked potentials did not predict neurologic injury. Loss of somatosensory evoked potentials had a high sensitivity (95%) but had low specificity (67%) because of peripheral nerve ischemia. Loss of motor evoked potentials recorded from the spinal cord had high specificity (100%) but a low sensitivity (46%) and was therefore not a reliable predictor of neurologic injury. Return of motor evoked potentials during reperfusion did not correlate with functional recovery. Motor evoked potentials stimulated in the cortex and recorded from the spinal cord had low overall accuracy (59%).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Utility of thermography in the diagnosis of lumbosacral radiculopathy.
We performed infrared telethermography in 55 patients with the clinical diagnosis of lumbosacral radiculopathy and in 37 normal controls. Five readers interpreted the thermograms in a blinded fashion. A moderate degree of agreement was noted in tests of intraobserver and interobserver variability. The sensitivity of thermography ranged from 78% to 94% compared with 81% to 92% for imaging studies and 77% for EMG. The specificity of thermography ranged from 20% to 44%. Thermography predicted the level of the radiculopathy correctly in less than 50% of cases. Thermography has little or no utility in the diagnosis of lumbosacral radiculopathy.
Adult↗
Drug-induced illness in the elderly.
The elderly are predisposed to adverse drug reactions because of age-related physiologic changes, interaction of one drug with another, and interaction between a drug and a coexisting medical condition. Recognition of such adverse reactions is essential, because many are reversible and many are even preventable. Assessment of clinical disorders in the elderly should include evaluation of drugs as a causal or aggravating factor. Careful choice and dosage of drugs in the elderly will minimize the likelihood of drug-induced illness.
Aged↗
Distinction between neoplastic and radiation-induced brachial plexopathy, with emphasis on the role of EMG.
The results of clinical, radiologic, and electrophysiologic studies are retrospectively reviewed for 55 patients with neoplastic and 35 patients with radiation-induced brachial plexopathy. The presence or absence of pain as the presenting symptom, temporal profile of the illness, presence of a discrete mass on CT of the plexus, and presence of myokymic discharges on EMG contributed significantly to the prediction of the underlying cause of the brachial plexopathy. The distribution of weakness and the results of nerve conduction studies were of no help in distinguishing neoplastic from radiation-induced brachial plexopathy.
Adult↗