Assessing South African medical interns' experience and confidence in managing obstetric emergencies.

BACKGROUND: Medical doctors in South Africa (SA) are required to complete a 2-year internship at training hospitals, including a 4-month rotation in obstetrics and gynaecology. Following this, doctors are allocated to community service posts, many of which are at district- and primary-level facilities where supervision is limited. Recent triennial Saving Mothers reports identify district hospitals (DHs) as the second leading site for maternal deaths of all causes, the leading site for maternal deaths secondary to obstetric haemorrhage, and the most likely site for the lack of a skilled doctor to be identified as a factor in deaths associated with caesarean delivery. OBJECTIVES: To describe the self-perceived readiness of medical interns completing their training to manage obstetric emergencies, based on the Essential Steps in the Management of Obstetric Emergencies modules in the Health Professions Council of South Africa's internship logbook. METHODS: This cross-sectional descriptive study assessed medical interns in the last 3 months of their training, using a self-administered online questionnaire. Data collection took place between October and December 2019. RESULTS: Cluster sampling of interns at training facilities throughout SA resulted in a total of 182 respondents from 17 hospitals in seven provinces in the country, with an overall response rate of 34.1%. Most interns had experience with and confidence in the management of miscarriage and hypertension in pregnancy. However, gaps in labour ward management, pregnancy-related sepsis and surgical skills were identified. Only 42.3% of respondents were confident in their ability to diagnose obstructed labour, 26.3% had performed an assisted delivery, 39.0% were confident in their knowledge of the indications for and contraindications to assisted deliveries, and 35.7% had been involved in the delivery of a baby with shoulder dystocia. Regarding pregnancy-related sepsis, 54.4% had experience with managing a wound abscess and 29.7% were confident managing puerperal endometritis. While 78.0% felt confident to perform a caesarean section (CS), only 28.6% had performed uterine compression suture for uterine atony at CS. Additionally, there was a statistically significant variation in scores between training hospitals. CONCLUSIONS: An incongruity exists between the shortcomings in DH obstetric services, the prioritisation of placement of community service doctors at primary healthcare facilities and DHs, and the self-perceived readiness of medical interns completing their training to manage obstetric emergencies safely. This situation highlights the importance of clinical support for junior doctors at DHs and standardisation of intern training at accredited facilities across SA.

Corollary discharge provides accurate eye position information to the oculomotor system.

The saccadic system accurately compensates for perturbations of eye position produced by microstimulation of the superior colliculus. This requires that information about the stimulation-induced change in eye position be provided by an extraretinal source--either proprioceptive endings in extraocular muscles or a centrally generated corollary discharge. It is shown that compensation remains intact after elimination of extraocular muscle proprioception, demonstrating that corollary discharge provides accurate eye position information.

The oculomotor periphery: the clinician's focus is no longer a basic science stepchild.

The study of the oculomotor periphery, the extraocular muscles and their orbital attachments, is undergoing a rapid expansion. This is an important progression for both basic and clinical communities as, for too long, the ophthalmologist has worked primarily in the periphery and the basic researcher has been occupied with study of the central components of the oculomotor system. From recent studies, it is clear that the morphology, cell and molecular biology, and genetics of the eye muscles and their corresponding motoneuron pools, and muscle attachments within the orbit are more complex than has heretofore been appreciated.

Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource-poor settings?

OBJECTIVES: To explore patient and health worker perspectives on adherence to tuberculosis preventive therapy (TBPT), and to derive lessons for improving access to care amongst human immunodeficiency virus (HIV) infected individuals in resource-poor settings. DESIGN: Both quantitative and qualitative methods were employed. Patient records were reviewed for HIV-positive individuals attending a hospital-based HIV clinic between January 2000 and March 2002. Eighteen patients and two health care workers underwent in-depth interviews exploring perspectives around adherence. RESULTS: Of 229 HIV-positive clinic attendees, 94 (41.0%) were eligible for TBPT. Of 87 patients initiating a 6-month TBPT course of isoniazid 300 mg daily, 41 (47.1%) completed TBPT. Of the 46 interrupters, 16 (34.7%) did not return to the clinic after receiving their first dose of TBPT. Barriers to adherence included fear of stigmatization, lack of money for food and transport, the belief that HIV is incurable, competition between Western and traditional medicine, and a reluctance to take medication in the absence of symptoms. Disclosure of HIV status, social and family support, and a supportive clinic environment positively influenced adherence. CONCLUSION: Interventions to improve the accessibility and quality of the care delivery system have the potential to support adherence to TBPT and other HIV care regimens, including antiretroviral therapy.

The value of wide-needle aspiration in the diagnosis of tuberculous lymphadenitis in Africa.

OBJECTIVES: To evaluate wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. SETTING: Department of Surgery, University Teaching Hospital, Lusaka, Zambia. PATIENTS: Three hundred and four patients presenting to one surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989-1990. DESIGN: Prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. MAIN OUTCOME MEASURES: Histology and mycobacterial culture of the surgically biopsied lymph node; HIV-1 serology; successful aspiration of material, naked-eye appearance of aspirate, presence of acid-fast bacilli and/or microscopic caseation in the aspirate. RESULTS: One hundred and eighty-eight out of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 out of 183 (84.7%) tested HIV-1-seropositive. Material was successfully aspirated from 180 out of 188 (95.7%) of patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 out of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 out of 155 (74.8%) aspirates from tuberculous nodes for which smears stained both by Ziehl-Nielsen and haematoxylin & eosin were available. CONCLUSIONS: It is recommended that all patients with suspected tuberculous lymphadenitis in Africa, undergo wide-needle aspiration before surgical biopsy or empirical treatment.

PIP: This study evaluated wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. 304 patients presenting to 1 surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989 and 1990 at the Department of Surgery, University Teaching Hospital, Lusaka, Zambia, were involved in this prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. Histology and mycobacterial culture of the surgically biopsied lymph node, HIV-1 serology, successful aspiration of material, naked-eye appearance of aspirate, and presence of acid-fast bacilli and/or microscopic caseation in the aspirate were the main outcome measures. 188 of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 of 183 (84.7%) tested HIV-1 seropositive. Material was successfully aspirated from 190 of 188 (95.7%) patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 of 155 (74.8%) aspirates from tuberculous nodes for which smears stained by both Ziehl-Nielsen and hematoxylin and eosin were available. It is recommended that all patients with suspected tuberculous lymphadenitis in Africa undergo wide-needle aspiration before surgical biopsy or empirical treatment.

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial.

OBJECTIVES: To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya. SUBJECTS: Six hundred and eighty-four HIV-1-infected adults. MAIN OUTCOME MEASURES: Development of tuberculosis and death. RESULTS: Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12). CONCLUSIONS: Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

Brainstem terminations of extraocular muscle primary afferent neurons in the monkey.

The central terminations of afferent nerve fibers from the extraocular muscles of the monkey were investigated by means of transganglionic transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA/HRP). Following injections of selected extraocular muscles with WGA/HRP, terminal labeling was apparent in the ipsilateral trigeminal sensory and cuneate nuclei. The density of trigeminal projections varied markedly from one rostrocaudal level to the next, being heaviest within the ventrolateral portion of pars interpolaris of the spinal trigeminal nucleus. A second extraocular muscle afferent representation was noted in ventrolateral portions of the cuneate nucleus. This projection was restricted to rostral portions of pars triangularis of the cuneate nucleus, partially overlapping the afferent termination from dorsal neck muscles. It is likely that some of the problems encountered in formulating conclusions regarding the functional role of extraocular muscle proprioception are due to a lack of detailed information of the central termination pattern of muscle afferents. Taken together, the present findings should provide a basis for further anatomical and physiological studies designed to elucidate the role played by extraocular muscle proprioceptors in vision and oculomotor control.

Neck muscle afferent projections to the brainstem of the monkey: implications for the neural control of gaze.

Brainstem projections of first-order afferent neurons that innervate the suboccipital muscles of the monkey have been determined by using the technique of transganglionic transport of wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA/HRP) and HRP. Neck muscle afferents distribute to several distinct regions located within the caudal brainstem and rostral spinal cord. Terminal labeling was heaviest within the ventral portion of the ipsilateral lateral cuneate nucleus. Muscle afferent terminals also distributed to ventrolateral portions of the pars triangularis division of the cuneate nucleus. Projections were consistent with the known somatotopic (i.e., both place and modality) organization of the cuneate nucleus. Moreover, neck muscle projections to the cuneate nucleus were, in part, coincident with those previously demonstrated for the extraocular muscles (Porter: J. Comp. Neurol. 247:133-143, '86). Sparse terminal projections were noted in the central cervical nucleus. In addition, light terminal labeling was present in group x of the vestibular complex and in an ill-defined region along the lateral margin of the brainstem. Present observations, which provide the first complete description of the central distribution of neck muscle afferent neurons in the primate, may contribute to the known substrate for eye/head coordination.

Localization of morphology of cat extraocular muscle afferent neurones identified by retrograde transport of horseradish peroxidase.

Afferent neurones that provide proprioceptive innervation extraocular muscles of the cat have been identified by means of retrograde axonal transport of horseradish peroxidase (HRP). Discrete injections of HRP into the medial rectus, lateral rectus, or retractor bulbi muscles labeled pseudounipolar neurons that were localized exclusively to the ipsilateral semilunar ganglion. The distribution of labeled neurons within the ganglion was consistent with its somatotopic organization with the majority found within the ophthalmic subdivision. Cell counts indicating approximately 90 labeled neurones per horizontal rectus muscle correlated well with earlier quantitative observations regarding the percentage of afferent fibers in oculomotor nerves and the number of proprioceptive terminals in the extraocular muscles. Neither the trigeminal mesencephalic nucleus nor the contralateral semilunar ganglion contained labeled neurones following injections of HRP into extraocular muscles. Consistent with other studies of spinal and cranial ganglia the contingent of pseudounipolar neurones present in the cat semilunar ganglion included both light and dark cell types. Light and electron microscope analysis of HRP-labeled neurones in combination with acetylcolinesterase (AChE) histochemistry revealed that only one of the two neuronal types, the light cell, subserves extraocular muscle proprioception. Our data support the hypothesis that ganglion neurone type and, more specifically, soma diameter, are important determinants of functional status.

Innervation and structure of extraocular muscles in the monkey in comparison to those of the cat.

Motoneurones that innervate the medial rectus, lateral rectus, and accessory lateral rectus muscles in the monkey have been identified and localized by retrograde transport of horseradish peroxidase. Medial rectus motoneurones were located within both dorsal and ventral regions of the oculomotor nucleus, with a differential distribution along the rostral-caudal axis of the nucleus. Lateral rectus motoneurones were located predominantly within the abducens nucleus, and were distributed throughout the rostral-caudal extent of the nucleus. Motoneurons that innervate the accessory lateral rectus muscle comprised a group of large cells located approximately 0.5 mm ventral to the rostral portion of the abducens nucleus, corresponding to the ventral abducens nucleus of Tsuchida ('06). The ventral subgroup of abducens motoneurones, which innervate both the lateral rectus and accessory lateral rectus muscles, thus do not occupy a motoneurones innervate the retractor bulbi muscle, to which the accessory lateral rectus muscle presumably is homologous. A few accessory lateral rectus motoneurones also were located within the abducens nucleus, overlapping the distribution of lateral rectus motoneurones. Electron microscope examination of the lateral rectus muscle revealed the presence of three morphological types of singly innervated muscle fibers and two morphological types of multiply innervated muscle fibers that exhibited a differential distribution within the orbital, intermediate, and global regions of the muscle. The accessory lateral rectus muscle resembled the global portion of the lateral rectus muscle in containing two morphological types of singly innervated fibers and one type of multiply innervated fiber. These findings indicate that the central differences in the brainstem locations of motoneurones that innervate the cat retractor bulbi and monkey accessory lateral rectus muscles are correlated with peripheral differences not only in the morphology, but also possibly in the mechanical roles, of the muscles they innervate. The accessory lateral rectus muscle thus appears to have evolved both structurally and functionally toward more of a role in patterned eye movement. Furthermore, with the phylogenetic regression of the retractor bulbi muscle, the various types of eye movement with which this muscle is associated in lower vertebrates may be assumed by the other extraocular muscles in higher mammals, including humans.

Morphological substrate for eyelid movements: innervation and structure of primate levator palpebrae superioris and orbicularis oculi muscles.

The levator palpebrae superioris and orbicularis oculi are antagonistic muscles that function during movements of the eyelid. The levator also functions in conjunction with superior and inferior rectus muscles in coordinated eye/lid movements. The present study examined the innervation and morphology of these muscles in Cynomolgous monkeys (Macaca fascicularis) in order to provide a better understanding of the anatomical substrate for lid movements. Motoneurons innervating the levator and orbicularis muscles were identified and localized by retrograde transport of WGA/HRP and HRP. Retrogradely labelled levator motoneurons were distributed bilaterally throughout the caudal central division of the oculomotor nucleus. A few labelled cells were also present within the contralateral superior rectus division, possibly because of the spread of tracer at the injection site. The possibility that individual motoneurons collateralize to innervate the levator muscle bilaterally was tested by using double retrograde labelling techniques. Doubly labelled levator motoneurons could not be detected by using a combination of tracers (HRP and Fast Blue). Motoneurons innervating the upper lid portion of the orbicularis oculi muscle were distributed within the dorsal subdivision of the ipsilateral facial motor nucleus, with a few neurons in the corresponding locus of the contralateral facial nucleus. Species differences in levator motoneuron distribution, particularly distinctions in lateral-eyed versus frontal-eyed mammals, are discussed in relation to the neural control of lid movements. The levator palpebrae superioris contains three of the same ultrastructurally defined types of singly innervated muscle fiber found in the global layer of other extraocular muscles and an additional, unique slow-twitch fiber type. Moreover, the multiply innervated fiber types so characteristic of the other extraocular muscles are conspicuously absent from levator muscles. Unlike the rectus and oblique extraocular muscles, the levator lacks a layered distribution of fiber types. The morphological profiles of levator muscle fiber types are such that they generally do not respect traditional fiber classification schemes, but are consistent with a role for the levator in sustained elevation of the lid. The orbicularis oculi muscle, by contrast, exhibited three distinct fiber types that resembled categories of skeletal muscle twitch fibers. One slow-twitch and two fast-twitch fiber types were noted. On the basis of oxidative enzyme profiles and mitochondrial content, the majority of orbicularis oculi fibers would be fatigue-prone, an assessment consistent with their rapid onset/offset of acti

Interconnections between the primate cerebellum and midbrain near-response regions.

The goal of this study was to determine the pattern of the connections between the midbrain and cerebellum that may play a role in the modulation of the near-response in the macaque. Injection of the retrograde tracer wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the physiologically identified midbrain near-response region, which includes the supraoculomotor area, labelled cells throughout the deep cerebellar nuclei. However, labelled cells were particularly concentrated in the ventrolateral corner of the contralateral posterior interposed nucleus and in the contralateral and, to a lesser extent, the ipsilateral fastigial nuclei. Subsequently, injections of WGA-HRP were used to define the midbrain terminations of the deep cerebellar nuclei. Fastigial nucleus injections labelled terminals in a band along the border between the oculomotor nucleus and the supraoculomotor area that included the Edinger-Westphal nucleus. Injections of the posterior interposed nucleus labelled terminals in the portion of the supraoculomotor area dorsal to the fastigial projection and did not involve the Edinger-Westphal nucleus. In both cases, the terminal label was primarily found contralaterally. In contrast, retrogradely labelled cells were primarily found ipsilaterally within the supraoculomotor area following cerebellar injections. Retrogradely labelled cells projecting to the deep nuclei were also found bilaterally in the anteromedian nucleus, along with sparse terminal label. Taken as a whole, these results demonstrate the presence of a highly specific pattern of labelling in the supraoculomotor area, which may indicate that the posterior interposed nucleus and the fastigial nucleus play different roles in the control of the near-response. Alternatively, these projections may subserve other functions, such as modulating the pupillary light reflex. The fact that the projection from the deep nuclei is primarily contralateral, while the supraoculomotor projection to the deep nuclei is primarily ipsilateral, suggests that this may not be a simple feedback system, but may instead be involved in balancing the gains in the two eyes. In sum, physiological experiments have indicated the presence of near-response neurons in the midbrain supraoculomotor area and have indicated that the cerebellum may play a role in modulating the components of the near-response, as well as activity in the intrinsic eye muscles. The present experiments suggest a pattern of connections that might subserve this cerebellar modulation.

Muscles of a different 'color': the unusual properties of the extraocular muscles may predispose or protect them in neurogenic and myogenic disease.

The rules that govern many aspects of skeletal muscle structure and function are very different for the extraocular muscle allotype. The myoblast lineages present in the extraocular muscle primordia are permissive for generation of an unusually wide range of fiber types. The balance that is struck between genetic specification and activity dependent factors in shaping fiber phenotype to suit the demands of complex visuomotor systems is not yet well defined. Because skeletal muscle has high energy demands, diversity in fiber types is needed to maximize efficiency; greater diversity in fiber composition then indicates a more diverse functional repertoire. Together, the characteristics of small motor unit size, precise dependence of muscle force upon motor neuron discharge rate, high contractile speed but low tension development, and contractile protein heterogeneity contribute toward the high precision and diversity that is required for eye movements. Finally, the structural and functional characteristics and plasticity of the individual extraocular muscle fiber types play an important role in determining their response to disease or manipulation. The lack of uniform responses across the muscle allotypes in disease, or in response to pharmaceutical or surgical interventions, requires that we obtain a better understanding of the fundamental differences that exist between muscle groups.

Aberrant reinnervation of facial musculature in a subhuman primate: a correlative analysis of eyelid kinematics, muscle synkinesis, and motoneuron localization.

A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zygomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.

Maladaptive neural compensatory mechanisms in Bell's palsy-induced blepharospasm.

We described four patients with Bell's palsy and blepharospasm and evaluated potential mechanisms that may be responsible for an apparent association between the two disorders. Eyelid movements in spontaneous blinks were studied by the search coil technique in patients with this novel disorder. Kinematic analyses documented bilateral eyelid spasm subsequent to unilateral Bell's palsy. The temporal interval between the onset of palsy and onset of blepharospasm was highly variable (weeks to > 20 years). Changes in the relationship between spontaneous blink peak velocity and amplitude, the main sequence, shared features previously found in uncomplicated Bell's palsy and blepharospasm patients. Furthermore, as in patients with typical Bell's palsy and idiopathic blepharospasm, both normal blinks and spasms were conjugate in spite of interocular differences in blink amplitude/peak velocity. We suggest that there is a correlation between the eyelid palsy and subsequent blepharospasm, and have designated this potentially new disease entity as Bell's palsy-induced blepharospasm. We propose a two-stage model for Bell's palsy-induced blepharospasm in which blink adaptive systems may produce the maladaptive consequence of eyelid spasms.

Kinematic analysis of eyelid movements in patients recovering from unilateral facial nerve palsy.

We assessed eyelid function by subjective clinical examination and quantitative means in patients recovering from facial nerve palsy. Electromagnetic search coil techniques were used to record the concurrent movements of the two eyelids to study alterations in blink main sequence (peak velocity versus amplitude) relationships and interocular differences in eyelid kinematics. After onset of unilateral palsy, the paresis of eyelid closure showed varying degrees of recovery. Adaptive increases in blink main sequence slope contributed to maximizing closure of the paretic eyelid. However, blink adaptation mechanisms must operate bilaterally, as there also was evidence of altered main sequence slope in the nonparetic eyelid. In general, main sequence slope was inversely related to the level of eyelid paresis. The highest indices of blink adaptation were in those patients with moderate paresis, and main sequence slope was decreased in those patients with increasing degrees of recovery. The assessment of eyelid function with search coil techniques provides a sensitive means of monitoring disease and treatment course. Data also aid understanding of adaptive gain control in the neural control of blink in health and disease.

Commentary: extraocular muscle sparing in muscular dystrophy: a critical evaluation of potential protective mechanisms.

Muscles or muscle groups exhibiting responses to neuromuscular disease that are unlike those of other skeletal muscles may provide novel information about pathogenesis leading to improved treatment strategies. The author's laboratory studies the relationship between the unique phenotype of the extraocular muscles and their selective sparing or targeting in neuromuscular disease. This commentary evaluates the evidence for and against four hypotheses for the selective protection of extraocular muscle in Duchenne muscular dystrophy (DMD) and merosin-deficient congenital muscular dystrophy (CMD).

Oxidative stress as a potential pathogenic mechanism in an animal model of Duchenne muscular dystrophy.

Dystrophin-deficiency results in degeneration of most, but not all, skeletal muscles. The mechanisms responsible for degeneration of limb muscle and sparing of extraocular muscle are not known. To address the notion that muscle pathology may be free radical-mediated, we evaluated antioxidant enzyme activities and lipid peroxidation products (TBARS) content in mdx and control mice. TBARS content and the activities of total superoxide dismutase, selenium dependent glutathione peroxidase, glucose-6-phosphate dehydrogenase and catalase were consistently higher in both affected and spared muscles of mdx mice. These data suggest that oxidative stress may be constitutively present in mdx muscle, but may not be the principal pathogenic mechanism. To further test the hypothesis of oxidative stress involvement in dystrophinopathies, control strain and mdx mice were subjected to chronic hyperoxia. The pattern of antioxidant enzyme activities and TBARS content from hyperoxic control strain mice was similar to that of normoxic mdx mice, suggesting that a similar level of oxidative stress was induced. In conclusion, this study has provided indirect evidence for oxidative stress in dystrophin-deficient muscle.

Extraocular muscle is spared despite the absence of an intact sarcoglycan complex in gamma- or delta-sarcoglycan-deficient mice.

Models of the dystrophin-glycoprotein complex do not reconcile the novel sparing of extraocular muscle in muscular dystrophy. Extraocular muscle sparing in Duchenne muscular dystrophy implies the existence of adaptive properties in these muscles that may extend protection to other neuromuscular diseases. We studied the extraocular muscle morphology and dystrophin-glycoprotein complex organization in murine targeted deletion of the gamma-sarcoglycan (gsg(-/-)) and delta-sarcoglycan (dsg(-/-)) genes, two models of autosomal recessive limb girdle muscular dystrophy. In contrast to limb and diaphragm, the principal extraocular muscles were intact in gsg(-/-) and dsg(-/-) mice. However, central nucleated, presumptive regenerative, fibers were seen in the accessory extraocular muscles (retractor bulbi, levator palpebrae superioris) of both strains. Skeletal muscles of gsg(-/-) mice exhibited in vivo Evans Blue dye permeability, while the principal extraocular muscles did not. Disruption of gamma-sarcoglycan produced secondary displacement of alpha- and beta-sarcoglycans in the extraocular muscles. The intensity of immunofluorescence for dystrophin and alpha- and beta-dystroglycan also appeared to be slightly reduced. Utrophin localization was unchanged. The finding that sarcoglycan disruption was insufficient to elicit alterations in extraocular muscle suggests that loss of mechanical stability and increased sarcolemmal permeability are not inevitable consequences of mutations that disrupt the dystrophin-glycoprotein complex organization and must be accounted for in models of muscular dystrophy.