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Treatment of spasmodic torticollis with local injections of botulinum toxin. One-year follow-up in 37 patients.

Thirty-seven patients with spasmodic torticollis (cervical dystonia) who received repeated local injections of botulinum toxin have been followed up for a mean period of 12.3 (10-29) months, during which time 138 treatment sessions were performed. Mean doses per muscle averaged 320 mouse units (mu; range 160-1000 mu botulinum toxin A prepared by CAMR, Porton Down, UK). Eighty-six per cent of patients experienced significant improvement of posture and 84% of those with pain had relief following the first injection. Muscular patterns of recurrent torticollis were relatively constant and in most patients efficacy was maintained with subsequent injections, while 15% of all follow-up sessions failed. Only 2 of 37 patients were consistent nonresponders; 22% and 10% of all sessions were complicated by transient dysphagia and weakness of neck muscles, respectively. It is concluded that local botulinum toxin injections can be a safe and efficaceous long-term treatment of spasmodic torticollis and that optimal doses should be between 200 and 400 mu/muscle.

Botulinum Toxins↗

Distribution of external cuneate nucleus afferents to the cerebellum: II. Topographical distribution and zonal pattern--an experimental study with radioactive tracers in the cat.

Small injections of tritiated leucine and the autoradiographic method were used to demonstrate efferents from restricted portions of the external cuneate nucleus (NCE) to the cerebellum. Sites of injection were analyzed by reference to the distribution of primary muscle afferents in NCE. On transverse sections, the silver deposits form longitudinal bands that, in certain regions, are packed together and label the entire surface of the granular layer; in other parts, they are separated by empty longitudinal bands. The longitudinal deposits are not continuous in the rostrocaudal direction. On the basis of the distribution of the longitudinal bands, 14 zones have been described for lobules II-VI, and 6 zones were recognized in lobules I, VIII, and the paramedian lobule. Afferents from NCE are distributed topographically. Regions of the nucleus receiving axial and neck muscles project mainly to vermal regions of lobules I-III, and to parts of lobules VIII and IX. Regions receiving afferents from forelimb muscles send their fibers preferentially to the vermian region of lobule V, to paravermian regions of lobules IV-VI, to parts of lobules VIII and IX, and to the paramedian lobule. These distributions in several respects are in agreement with the somatotopical maps of the cerebellum. However, other features support a "mosaic" arrangement: efferents from a region of NCE are distributed over several distinct sites of the cortex and efferents from different parts of the nucleus also converge to neighboring cortical regions.

Afferent Pathways↗

Operant conditioning of head-waving in Aplysia. III. Cellular analysis of possible reinforcement pathways.

Operant conditioning of the head-waving response in Aplysia, as well as conditioning of the electrical activity of identified neck muscles, can be induced readily when bright light is used as aversive reinforcement (Cook and Carew, 1986, 1989b). A cellular analysis of this type of operant conditioning requires an understanding of the neural circuitry that underlies the reinforcement pathways involved in the conditioning. In the present paper we describe a cellular analysis of possible reinforcement pathways that mediate the aversive effects of bright light in the CNS of Aplysia. Using a semi-intact "split-body" preparation, we explored the effects of bright light on the operant response pathway by recording intracellularly from identified pedal neck and body wall motor neurons, which contribute to the operant response. In these experiments we identified 2 light-sensitive pathways. One pathway, from the eyes and rhinophores, mediated functional inhibition of light-induced excitation of pedal motor neurons. The other pathway, from the oral veil (cerebral ganglion nerves C1-C3) mediated significant excitation of the same motor cells. Randomly occurring blank trials ruled out the possibility that the light-induced effects were due to sampling bias. Finally, surgical isolation of the CNS from the periphery showed that none of the effects of light were due to direct illumination of central neurons. This identification of candidate reinforcement pathways will facilitate a cellular analysis of operant conditioning of head-waving in Aplysia.

Animals↗

A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy.

PURPOSE: Locoregional tumor control for locally advanced cancers with radiation therapy has been unsatisfactory. This is in part associated with the phenomenon of tumor hypoxia. Assessing hypoxia in human tumors has been difficult due to the lack of clinically noninvasive and reproducible methods. A recently developed positron emission tomography (PET) imaging-based hypoxia measurement technique which employs a Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) tracer is of great interest. Oxygen electrode measurements in animal experiments have demonstrated a strong correlation between low tumor pO(2) and excess (60)Cu-ATSM accumulation. Intensity-modulated radiation therapy (IMRT) allows selective targeting of tumor and sparing of normal tissues. In this study, we examined the feasibility of combining these novel technologies to develop hypoxia imaging (Cu-ATSM)-guided IMRT, which may potentially deliver higher dose of radiation to the hypoxic tumor subvolume to overcome inherent hypoxia-induced radioresistance without compromising normal tissue sparing. METHODS AND MATERIALS: A custom-designed anthropomorphic head phantom containing computed tomography (CT) and positron emitting tomography (PET) visible targets consisting of plastic balls and rods distributed throughout the "cranium" was fabricated to assess the spatial accuracy of target volume mapping after multimodality image coregistration. For head-and-neck cancer patients, a CT and PET imaging fiducial marker coregistration system was integrated into the thermoplastic immobilization head mask with four CT and PET compatible markers to assist image fusion on a Voxel-Q treatment-planning computer. This system was implemented on head-and-neck cancer patients, and the gross tumor volume (GTV) was delineated based on physical and radiologic findings. Within GTV, regions with a (60)Cu-ATSM uptake twice that of contralateral normal neck muscle were operationally designated as ATSM-avid or hypoxic tumor volume (hGTV) for this feasibility study. These target volumes along with other normal organs contours were defined and transferred to an inverse planning computer (Corvus, NOMOS) to create a hypoxia imaging-guided IMRT treatment plan. RESULTS: A study of the accuracy of target volume mapping showed that the spatial fidelity and imaging distortion after CT and PET image coregistration and fusion were within 2 mm in phantom study. Using fiducial markers to assist CT/PET imaging fusion in patients with carcinoma of the head-and-neck area, a heterogeneous distribution of (60)Cu-ATSM within the GTV illustrated the success of (60)Cu-ATSM PET to select an ATSM-avid or hypoxic tumor subvolume (hGTV). We further demonstrated the feasibility of Cu-ATSM-guided IMRT by showing an example in which radiation dose to the hGTV could be escalated without compromising normal tissue (parotid glands and spinal cord) sparing. The plan delivers 80 Gy in 35 fractions to the ATSM-avid tumor subvolume and the GTV simultaneously receives 70 Gy in 35 fractions while more than one-half of the parotid glands are spared to less than 30 Gy. CONCLUSION: We demonstrated the feasibility of a novel Cu-ATSM-guided IMRT approach through coregistering hypoxia (60)Cu-ATSM PET to the corresponding CT images for IMRT planning. Future investigation is needed to establish a clinical-pathologic correlation between (60)Cu-ATSM retention and radiation curability, to understand tumor re-oxygenation kinetics, and tumor target uncertainty during a course of radiation therapy before implementing this therapeutic approach to patients with locally advanced tumor.

Algorithms↗

Invasive thymoma (a case report).

A 10-year old Nigerian boy was admitted to hospital with a history of swelling in the neck, change of voice, dysphagia and dyspnoea of 2 weeks duration. He died on the 2nd day of admission. Autopsy revealed a thymoma infiltrating the thyroid, trachea and neck muscles and transforming the tracheal lumen into a slit like space. The condition is considered worthy of record on account of its rarity and of the short clinical course terminating in death. The authors feel that the most important factor in determining the prognosis of thymoma is the presence or absence of gross invasion.

Airway Obstruction↗

Development of the spinal tract of the trigeminal nerve and its relation to early fetal behavior in rats under normal and hypothyroid conditions.

The effects of hypothyroidism on the development of the spinal tract of V and its relation to early fetal behavior were studied in rats from day 16 through day 20 of gestation. Hypothyroidism was induced by the administration of 0.5% Propylthiouracil mixed with rat diet beginning from day seven through term. The thyroid glands of treated and untreated control fetuses of the same age groups were examined in histologic sections. The position, size, and caudal extent of the ophthalmic and maxillomandibular divisions of the spinal tract of V were analyzed in detail with the aid of graphic reconstructions from serial sections of representative cases of both control and experimental fetuses. The ophthalmic and maxillomandibular divisions of the spinal tract of V at 15 days in the control group of fetuses extended into the second and fourth cervical spinal segments respectively, while by 19 days, both divisions of the spinal tract of V extended as far as the fourth cervical segment. In the treated group of fetuses, the ophthalmic and maxillomandibular divisions were greatly reduced in area as well as in their caudal extent into upper cervical levels compared to control groups at corresponding stages of development. At the behavioral level, the frequency of individual movements of the head, forelimbs and mouth in the treated group of fetuses was significantly reduced compared with control fetuses of the same age. Combination types of movements of head, mouth and forelimbs were severely affected both quantitatively and qualitatively in the treated group from day 18 of gestation age. It could be demonstrated that the caudal extent of the spinal tract of V corresponded very closely to the behavior repertoire seen in the fetuses of that age. We propose (1) that the spinal tract of V, in its relation with the upper cervical spinal cord levels which contain motor neurons of the spinal accessory nucleus and motor neurons which innervate the dorsal neck muscles, could play a decisive role in the integration of head and shoulder movements in early stages of development, and (2) that thyroid hormone may play a crucial role in the normal development of the spinal tract of V which is manifest in its caudal growth into upper cervical levels of the spinal cord.

Animals↗

[An unusual association of myasthenia gravis and Parkinsonism in a female patient with tuberculous lymphadenitis].

We report on a female patient who had a tumour below the mandibular, on the right side of the neck, aged 70 years. When she was 74 years old easy discomfort characterized by trembling of the hands while resting and moving to the target as well as a certain stiffness of the neck, appeared. Three years later, at the age of 77, she felt fatigue, ptosis, double vision, weakness of the jaws while chewing, speech and swallowing disturbances, and weakness of the legs, that led to disability. In such state of health the patient was admitted to hospital for medical examination. Hypomimia, rigor of the neck muscles, vesting tremor, and, above all, clearly marked signs of myasthenic weakness and fatigue of the extraocular, masseteric, mimic, and bulbar muscles and those of the limbs, but in a lesser degree, were found. With Tensilon test we registered a positive response, and by an electrophysiological examination we defined a myasthenic decrement under the repetitive stimulus. Biopsy of submandibular tumour and histologic analysis indicated tuberculous lymphadenitis. Most symptoms of the disease disappeared during the treatment with anticholinesterase drugs and amantadine.

Aged↗

Effects of chronic hyperglycemia on electrocortical activity states in unanesthetized fetal lambs.

Electrocortical activity (ECoG), tracheal pressure and nuchal muscle activity were recorded in utero in 8 chronically hyperglycemic and 10 control unanesthetized fetal lambs to investigate the effects of chronic hyperglycemia on fetal electrocortical activity states. The chronically hyperglycemic state, induced by alloxan administered to the ewes, existed for at least 40 days prior to the experiments. The mean duration of episodes of high voltage (HV) ECoG was significantly increased in the hyperglycemic group (mean +/- SD: 21.8 +/- 9.2 min) compared with the control group (14.8 +/- 3.3 min), but the incidence of low voltage (LV) ECoG was not different between the groups. ECoG power spectra were not different between the groups. During LV ECoG, the proportions of time with neck movements were significantly less in the hyperglycemic than in the control group. No difference in percentages of time with long neck muscle activity was seen during the HV state in both groups. The incidence of breathing movements was equal in both groups, during HV as well as LV ECoG. No differences in breathing interval were observed.

Animals↗

The second kindred with autosomal dominant distal myopathy linked to chromosome 14q: genetic and clinical analysis.

BACKGROUND: Distal myopathies (MPDs) are genetically heterogeneous. Genetic causes within this subgroup of muscle disorders remain largely unknown. An MPD linked to chromosome 14q11-q13 (MPD1) is rare, and to our knowledge, only one family with definitive linkage has been described. OBJECTIVE: To describe the results of clinical and genetic analysis of the second kindred with MPD1. PATIENTS AND METHODS: We have identified a family with an MPD segregating in an autosomal dominant fashion. We tested linkage to previously identified genetic loci on chromosomes 2p, 2q, and 14q. The coding sequence of PABP2 (the polyadenylate-binding protein 2 gene) was analyzed. RESULTS: Every affected individual had selective weakness of foot extensors, with the average age of symptom onset at 20 years. Some patients also had proximal weakness, but none had signs of finger or hand extensor muscle involvement, even in advanced stages of the disease. Two typically affected individuals had signs of idiopathic dilated cardiomyopathy. Genetic analysis detected a tight linkage to chromosome 14q11-q13. Recombination at the telomeric end of the 14q11-q13 locus was found in an unaffected individual who was not considered to be at risk, potentially reducing the locus interval by 2 centimorgans. No mutations in the PABP2 gene were identified. CONCLUSIONS: To our knowledge, our described family is only the second known kindred with a chromosome 14-linked MPD in whom the linkage has been unequivocally established. We did not detect signs of involvement of hand or finger extensors and neck muscles, seen in the original family with MPD1. The degree and frequency of proximal weakness seem to be more prominent than in other patients with MPD1. Haplotype analysis suggests that the gene is located between polymorphic microsatellite markers D14S283 and D14S1034 on chromosome 14q11-q13. The presence of cardiomyopathy in some affected individuals may help in the identification of candidate genes.

Adult↗

Do neck-proprioceptive and caloric-vestibular stimulation influence covert visual attention in normals, as they influence visual neglect?

Neck-proprioceptive and caloric-vestibular stimulation have been shown to ameliorate the spatial bias exhibited by patients suffering from unilateral visual neglect. These interventions might in principle have their effect by biasing covert attention towards the neglected side. If so, the same interventions should also modulate covert attention in neurologically-intact subjects. However, we demonstrate here that neither neck-proprioception (vibration of left neck muscles) nor caloric-vestibular stimulation (injection of iced water into the left ear) affect covert visual attention in healthy individuals. These results from normals may distinguish between different accounts for unilateral neglect in patients. In particular, they argue against explanations of neglect solely in terms of a pathological misperception of body orientation within an otherwise normal neural representation of space.

Adult↗

Condylar resorption during active orthodontic treatment and subsequent therapy: report of a special case dealing with iatrogenic TMD possibly related to orthodontic treatment.

A 28-year-old female underwent orthodontic treatment for approximately 22 months. During the later stages of this treatment, the patient reported right shoulder and neck-muscle pain. In addition, temporomandibular joint disorder (TMD) with a 'clicking' sound during mastication commenced 5 months prior to treatment completion. Specific medication to deal with these symptoms was suggested by medical specialists, as were some stress-relief methods, although the pain still progressed, and subsequent clinical and radiographical examinations were undertaken by another orthodontist. Right mandibular condylar resorption was observed from both the panorex and temporomandibular joint (TMJ) radiographs. No clinical signs of rheumatic disease were observed, although bruxism was noted. Following the termination of the orthodontic treatment by the second practitioner, the patient was treated with splint therapy 1 month subsequent to which, the previous symptoms of pain in the shoulder and neck, and the clicking sound during mastication had subsided. During the 14-month period of splint therapy and follow-up, new bone growth in the right condyle was observed from radiographs.

Adult↗

Responses of neurons in the central cervical nucleus of the rat to proprioceptive and vestibular inputs.

Activity of neurons in the central cervical nucleus (CCN) was recorded extracellularly in decerebrate, immobilized rats. Neurons were identified by their antidromic response to electrical stimulation of the contralateral superior cerebellar peduncle. Stimulation of the ipsilateral dorsal neck muscles (m. biventer cervicis and complexus [BCC]; m. splenius [S]) by a single electric pulse evoked a short-latency (approximately 1 ms) excitatory response in the majority of CCN neurons. The response was usually followed by a period of inhibition of the resting discharge (approximately 20 ms). Stimulation of the contralateral BCC or S usually produced only inhibition of the resting discharge (approximately 20 ms). Mechanical stretching of BCC or S resulted in activation (about 100% increased firing rate) of the ipsilateral CCN neurons, lasting for the duration of the stretch. A pronounced dynamic component, i.e. an extra-excitation at the beginning of the stretch and inhibition after termination of the stretch, was also observed. Stroking and pinching of the skin in the neck region affected the tested CCN neurons, while cutaneous stimuli at other sites of the body were inefficient. Stimulation of the vestibular receptors was performed in two ways. (i) Unilateral galvanic stimulation of the labyrinths by constant current pulses through the external acoustic meatus affected all CCN neurons tested. Contralateral stimulation with negative current was found to be most efficient; it produced excitation followed by inhibition. (ii) Natural vestibular stimulation was performed by rotating the animal in the transverse plane (roll, +/- 10 degrees) or the sagittal plane (pitch, +/- 5 degrees). Sinusoidal movements (0.5-1 Hz) or trapezoid movements were applied. Sinusoidal roll tilt evoked responses in all neurons tested, with a peak discharge during contralateral rolling or at the moment of transition from the ipsi- to contralateral position. All tested CCN neurons also responded statically to roll tilt, i.e. their tonic activity increased with up to 65%, of which the majority (80%) responded in the continuously maintained contralateral roll tilt position compared to the ipsilateral. Sinusoidal pitch tilt also affected all tested neurons, although the reaction was smaller than compared to roll. They usually responded by increasing their firing rate when moving towards the nose-down position. A static response (40-60% difference in the firing rate between the extreme pitch positions) was observed in some neurons. No tested neurons showed any clear rhythmic modulation during either spontaneous or induced, real or fictive locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Differential effectiveness of EMG-feedback versus combined EMG-feedback and relaxation instructions in the treatment of tension headache.

After a 2 1/2 week baseline period 18 muscle tension headache patients were randomly assigned to one of three conditions: waiting list, formal EMG-feedback training, combined training of EMG-feedback and progressive relaxation. Patients in the two treatment conditions obtained 12 training sessions and returned 3 months after treatment for a follow-up session. Both treatment conditions were equivalent in their effect on EMG of m. frontalis and on headache scores, against stability for waiting list patients as observed in a separate analysis. Changes over treatment in both parameters were significantly correlated. Among changes in headache subparameters, the only significant correlation with changes in frontalis EMG was found for duration of pain. In both treatment conditions a generalizing effect to neck muscles was observed. Among personality variables decreases were found in neuroticism and somatization at follow-up for the combined training conditions, whereas the EMG-feedback alone condition remained unaltered. The combined training condition also proved superior in reducing operant pain behavior.

Adolescent↗

Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats.

The hypoglossal motor nucleus innervates the genioglossus (GG) muscle of the tongue, a muscle that helps maintain an open airway for effective breathing. Rapid-eye-movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity even during strong reflex stimulation such as by hypercapnia, effects that can predispose to sleep-related breathing problems in humans. We have developed an animal model to chronically manipulate neurotransmission at the hypoglossal motor nucleus using in vivo microdialysis in freely behaving rats. This study tests the hypothesis that glycine receptor antagonism at the hypoglossal motor nucleus, either alone or in combination with GABAA receptor antagonism, will prevent suppression of GG activity in natural REM sleep during room air and CO2-stimulated breathing. Rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) and strychnine (glycine receptor antagonist, 0.1 mM) either alone or combined with bicuculline (GABAA antagonist, 0.1 mM) during room air and CO2-stimulated breathing. Compared to ACSF controls, glycine receptor antagonism at the hypoglossal motor nucleus increased respiratory-related GG activity in room air (P = 0.010) but not hypercapnia (P = 0.221). This stimulating effect of strychnine in room air did not depend on the prevailing sleep-wake state (P = 0.625) indicating removal of a non-specific background inhibitory glycinergic tone. Nevertheless, GG activity remained minimal in those REM sleep periods without phasic twitches in GG muscle, with GG suppression from non-REM (NREM) sleep being > 85 % whether ACSF or strychnine was at the hypoglossal motor nucleus or the inspired gas was room air or 7 % CO2. While GG activity was minimal in these REM sleep periods, there was a small but measurable increase in GG activity after strychnine (P < 0.05). GG activity was also minimal, and effectively abolished, in the REM sleep periods without GG twitches with combined glycine and GABAA receptor antagonism at the hypoglossal motor nucleus. We conclude that these data in freely behaving rats confirm that inhibitory glycine and GABAA receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but that such inhibitory mechanisms make only a small contribution to the marked suppression of GG activity and reflex responses observed in periods of natural REM sleep.

Amino Acids↗

Lymph nodes of the neck: evaluation with US.

Ultrasound (US) proved highly effective for detection, localization, and delineation of enlarged lymph nodes of the neck. Infiltration of adjacent structures, specifically the common, internal, and external carotid arteries, and the neck muscles was reliably demonstrated. Benign and malignant lymph node enlargement could not be differentiated. US examinations changed the operative course of 56% of patients studied. In 41%, a more radical operative procedure was performed than was previously planned; in 14%, US demonstrated inoperability. Small-parts US is a very useful adjunct to current imaging techniques of cervical lymph node disease.

Humans↗

A groove observed in the face of an old man who probably died from acute asphyxia.

A continuous, horizontal groove about 0.7 cm wide was observed on the nape and lower part of the face of a 93-year-old man. The groove started from one corner of the mouth, traversed the nape, and reached the other corner of the mouth. It was most conspicuous at the nape. The mark was considered to have been produced by an electric cord. No facial congestion was noted, however, a few petechiae were present in the conjunctivae. There were no wounds in the front of the neck, while small hemorrhages were noted in the neck muscles. The right 2nd through 6th ribs were fractured and slight hemorrhage was observed in the overlying muscle. There were no pathologic changes accounting for death. The presence of the so-called triad for an acute death suggested strongly that the most likely cause of death was acute asphyxia. The relationship between the cause of death and the mark was the matter at issue. The mark may have been produced by a hanging in an unusual position, but there was no indication that a hanging was performed. For a ligature mark due to strangulation, the level was too high. The possibility that the mark was produced when the victim was gagged seemed to be very low. Thus, it could not be confirmed whether the groove had any relation with a fatal assault. Reflex cardiac arrest by vagal stimulation when the neck was compressed was the most likely cause of death.

Acute Disease↗

Statistical analysis of an urban population of 236 patients with head and neck pain. Part I. Patient profile.

A large group of patients (236) was examined for myofascial pain dysfunction syndrome. The parameters used for diagnosis of the syndrome were pain and tenderness in the head and neck muscles and temporomandibular joint, joint sounds, and limited function. It was found that the demographic profile of our patient population did not vary greatly from those reported previously in other studies. However, we did examine more details of the patients' backgrounds than any other single study. The relationships of age, sex, occupation, marital status, emotional stress, and head trauma were discussed.

Adolescent↗