Biomedical subjects
Publications and source records attributed to T D Heiman-Patterson.
Neuroleptic malignant syndrome and malignant hyperthermia share two cardinal clinical features: hypothermia and rigidity. Both syndromes can result in rhabdomyolysis and have high mortality rates if left untreated. This article reviews each syndrome and its pathogenesis and treatment.
Ca(2+)- and halothane-induced Ca(2+) release and Na+ currents are modulated by free fatty acids (FAs). FA modulation of ion currents may have important implications for general muscle physiology and skeletal muscle disorders, including malignant hyperthermia (MH).
We reviewed retrospectively 114 prednisone dose reduction attempts in 63 myasthenic patients. Dose reduction was considered successful if a patient remained asymptomatic for more than 1 year on no prednisone or a stable low dose of prednisone. Successful dose reduction attempts were more common in patients taking azathioprine, but thymectomy did not influence taper outcome. Slower rate of dose reduction and higher ending dose of prednisone improved the chance of success.
We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the "cramp-fasciculation syndrome."
Since the relationships between traditional assessments in ALS patients have not been defined, three clinical and four electrophysiological assessments were performed in a cross-sectional study of 87 ALS patients. The clinical assessments produced Norris ALS scores, muscle strength scores and illness durations (DUR). The electrophysiological assessments produced scores for motor unit interference pattern, denervation potentials, compound muscle action potential, and fasciculations. The individual muscle scores were averaged to produce mean scores, and Spearman rank correlations were performed on the mean scores. The association between Norris ALS and mean muscle strength (MMS) scores is significant (p less than .001, rs = 0.84), and these scores are significantly correlated with mean interference pattern (0.77, 0.82), mean denervation potential (-0.63, -0.70), and mean compound muscle action potential scores (0.55, 0.60), respectively. Correlations between IP and DP scores (-0.71), IP and CMAP scores (0.62), and DP and CMAP (-0.56) scores are also significant. Scatterplots of the data and regression lines suggest linear relationships between each of these assessments. Illness duration and fasciculation scores are not strongly correlated (rs less than 0.55) with any of the other clinical or electrophysiological assessments.
In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations.
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The association of malignant hyperthermia (MH) with neuromuscular disorders has been recognized since 1970. These disorders include central core disease, Duchenne muscular dystrophy, myotonia congenita, myotonic dystrophy, nonspecific myopathies, and King-Denborough syndrome. In order to assess the anesthetic risk of MH in the neuromuscular population, we performed halothane and caffeine contracture testing for MH susceptibility on biopsied muscle removed from 25 consecutive neuromuscular patients during diagnostic evaluation. Positive contracture tests were found in 7 of 18 patients with myopathic disorders and 3 of 7 patients with neurogenic disorders. Two of our patients had anesthetic events suggesting MH. These findings suggest that myopathic and neuropathic disorders share pathogenic mechanisms with MH, resulting in positive contracture tests and possibly leading to clinical events during anesthesia. Although there is controversy regarding the interpretation of a positive contracture test, contracture testing remains the most widely accepted test for MH susceptibility. Thus, a variety of neuromuscular disorders may be associated with MH susceptibility, and caution should be exercised during anesthesia in this group of patients.
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The relationship between neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) was investigated using the in vitro skeletal muscle contracture test to screen for MH-susceptibility in NMS patients. The maximum contracture tension which developed following exposure to halothane (1-3%), and incremental doses of fluphenazine (0.2-25.6 mM) was measured in muscle obtained from seven NMS, six MH, and six control patients. Comparison of the cumulative responses to fluphenazine revealed no significant differences among the groups. However, the response (mean +/- SEM) to halothane in the NMS group (1.7 +/- 0.7 g), which was similar to the response in the MH group (1.5 +/- 0.2 g), was significantly greater than the response found in controls (0.2 +/- 0.1 g). In addition, five of seven NMS patients could be diagnosed as MH-susceptible, based on the development of muscle contractures greater than 0.7 g in response to 1-3% halothane. In contrast, none of the controls were MH-susceptible. These findings appear to correlate with clinical evidence suggesting an association between NMS and MH.
The primate cochlear nuclear complex exhibits several characteristic morphological differences in the various primate families from Lorisidae through Hominidae. The most striking differences occur in the organization of the dorsal cochlear nucleus in which the laminar pattern becomes progressively obscured. Granule cells form an external granular layer as well as being intermixed within the molecular and pyramidal layers in slow lorises and squirrel and rhesus monkeys. Whereas a prominent external granular layer remains in chimpanzees, granule cells are scant in other portions of the nucleus. Human adults lack an external granular layer. A small number of granule cells occur but with inconstant distribution. Primates lack the linear array of pyramidal cells oriented perpendicularly to the epithelial surface as seen in cats. The granule cell layer exhibits similar regression in development of the human cochlear complex. The external granular layer is prominent in the fetus but rapidly decreases in size after birth. It achieves its adult form prior to 18 months. The data suggest that neuronal attrition, or programmed cell death, may be the major mechanism accounting for the alterations that occur in the human granule cell layer. Other differences in cytoarchitecture, within the great apes and humans, include decreases in the small and giant cell populations of the cochlear complex. These changes, in consort with the organizational changes and reduction of granule cells as noted above, suggest a trend towards reduced intranuclear integration at the level of the cochlear nucleus coupled with encephalization of the auditory system.
Lethargy, marked muscle weakness and rigidity, a maximal temperature of 40 degrees C, and a maximal creatine kinase value of 17,240 IU/liter developed in a 36-year-old woman following treatment with several neuroleptics. Initial treatment with dantrolene was unsuccessful. The patient's condition improved gradually over a 10-day period with no specific therapy. Muscle biopsy revealed a contracture pattern diagnostic of malignant hyperthermia susceptibility, as well as abnormal sensitivity to fluphenazine. This report may be the first description of a patient with neuroleptic malignant syndrome in whom muscle biopsy response similar to that seen in malignant hyperthermia occurred and documents that dantrolene is not uniformly successful therapy for this syndrome.
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The King-Denborough syndrome (KDS) is characterized by dysmorphic features, myopathy, and malignant hyperthermia (MH). Physiologic contracture testing for MH susceptibility has not been reported in KDS. A young boy with KDS underwent muscle biopsy evaluation at age 3 years that documented an abnormal contracture response to halothane, indicating MH susceptibility. Histopathology demonstrated small type II fibers associated with type I hypertrophy. Contracture testing of muscle obtained from the patient's mother was positive, while a sibling's test was negative. This case is the first to demonstrate susceptibility to MH with KDS by using physiologic contracture testing. The presence of positive MH results in both the patient and his mother suggest one of the following: (1) KDS may be part of the spectrum of autosomal dominantly inherited MH; (2) the locus for MH and for KDS may be linked closely and inherited concurrently, or; (3) the association of MH and KDS may be coincidental.
To evaluate malignant hyperthermia (MH) susceptibility in X-linked muscular dystrophies, halothane and caffeine contracture tests were performed on muscle fiber bundles from five patients with Duchenne muscular dystrophy (DMD) and two patients with Becker muscular dystrophy (BMD). Two DMD patients and one BMD patient had positive contracture tests. Since a positive contracture test is currently the best indicator of anesthetic susceptibility in the MH population, and episodes of MH in dystrophic patients have been reported, patients with DMD and BMD may be at risk for developing similar anesthetic complications. Awareness of this potential anesthetic risk is of importance because orthopedic interventions are increasingly more common in these patients.