Cortical stimulation leads to shortened myelin sheaths and increased axonal branching in spared axons after cervical spinal cord injury.

Neural activity and learning lead to myelin sheath plasticity in the intact central nervous system (CNS), but this plasticity has not been well-studied after CNS injury. In the context of spinal cord injury (SCI), demyelination occurs at the lesion site and natural remyelination of surviving axons can take months. To determine if neural activity modulates myelin and axon plasticity in the injured, adult CNS, we electrically stimulated the contralesional motor cortex at 10 Hz to drive neural activity in the corticospinal tract of rats with sub-chronic spinal contusion injuries. We quantified myelin and axonal characteristics by tracing corticospinal axons rostral to and at the lesion epicenter and identifying nodes of Ranvier by immunohistochemistry. Three weeks of daily stimulation induced very short myelin sheaths, axon branching, and thinner axons outside of the lesion zone, where remodeling has not previously been reported. Surprisingly, remodeling was particularly robust rostral to the injury which suggests that electrical stimulation can promote white matter plasticity even in areas not directly demyelinated by the contusion. Stimulation did not alter myelin or axons at the lesion site, which suggests that neuronal activity does not contribute to myelin remodeling near the injury in the sub-chronic period. These data are the first to demonstrate wide-scale remodeling of nodal and myelin structures of a mature, long-tract motor pathway in response to electrical stimulation. This finding suggests that neuromodulation promotes white matter plasticity in intact regions of pathways after injury and raises intriguing questions regarding the interplay between axonal and myelin plasticity.

Data processing techniques impact quantification of cortico-cortical evoked potentials.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) are a common tool for probing effective connectivity in intracranial human electrophysiology. As with all human electrophysiology data, CCEP data are highly susceptible to noise. To address noise, filters and re-referencing are often applied to CCEP data, but different processing strategies are used from study to study. NEW METHOD: We systematically compare how common average re-referencing and filtering CCEP data impacts quantification. RESULTS: We show that common average re-referencing and filters, particularly filters that cut out more frequencies, can significantly impact the quantification of CCEP magnitude and morphology. We identify that high cutoff high pass filters (> 0.5 Hz), low cutoff low pass filters (< 200 Hz), and common average re-referencing impact quantification across subjects. However, we also demonstrate that the presence of noise may impact CCEP quantification, and preprocessing is necessary to mitigate this. We show that filtering is more effective than re-referencing or averaging across trials for reducing most common types of noise. COMPARISON WITH EXISTING METHODS: These results suggest that existing CCEP processing methods must be applied with care to maximize noise reduction and minimize changes to the data. We do not test every available processing strategy; rather we demonstrate that processing can influence the results of CCEP studies. We emphasize the importance of reporting all processing methods, particularly re-referencing methods. CONCLUSIONS: We propose a general framework for choosing an appropriate processing pipeline for CCEP data, taking into consideration the noise levels of a specific dataset. We suggest that minimal gentle filtering is preferable.

Functions of mammalian spinal interneurons during movement.

The major recent advances in understanding the role of spinal neurons in generating movement include new information about the modulation of classic reflex pathways during fictive locomotion and in response to pharmacological probes. The possibility of understanding movements in terms of spinal representations of a basic set of movement primitives has been extended by the analysis of normal reflexes. Recordings of the activity of cervical interneurons in behaving monkeys has elucidated their contribution to generating voluntary movement and revealed their involvement in movement preparation.

Serial changes in bone mineral density and bone turnover after correction of secondary hyperparathyroidism in a patient with pseudohypoparathyroidism type Ib.

Pseudohypoparathyroidism (PHP) is a disorder characterized by hypocalcemia and secondary hyperparathyroidism caused by primarily renal resistance to the effects of parathyroid hormone (PTH). However, as an indication of normal PTH responsiveness in bone, some patients with PHP develop skeletal disease because of longstanding secondary hyperparathyroidism. A patient is described with hypocalcemia, hyperphosphatemia, marked secondary hyperparathyroidism, and an increased alkaline phosphatase level. Subsequent evaluation revealed a diagnosis of PHP type Ib. The patient had radiographic evidence of skeletal disease caused by secondary hyperparathyroidism. A urinary level of N-telopeptide cross-links of type I collagen (NTX) was elevated markedly. Bone mineral density (BMD) was in the normal range at all measured sites, with BMD at the spine being higher than at the femur and distal radius. Treatment was initiated with calcium and calcitriol. Seven months later, calcium and PTH levels had normalized. The level of urinary NTX fell by 83%. Spinal BMD improved by 15%, and BMD at the femoral neck improved by 11%. Radial BMD was unchanged. This case emphasizes the importance of evaluating patients with PHP for hyperparathyroid bone disease and shows that correction of secondary hyperparathyroidism in patients with PHP can result in a significant suppression of previously accelerated bone turnover and to substantial gains in BMD at sites containing a major percentage of cancellous bone. The case also implies that assessment of bone turnover with urinary NTX and measurement of BMD with dual-energy X-ray absorptiometry (DEXA) may be useful in following the response of the skeleton to therapy in these patients and suggests the need for more studies of both NTX and BMD in patients with PHP.

A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections.

BACKGROUND: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations. METHODS: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained. RESULTS: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases. CONCLUSIONS: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.

MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.

OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases.

OBJECTIVE: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS). METHOD: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities. RESULTS: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure. CONCLUSIONS: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies.

Distributed processing in the motor system: spinal cord perspective.

Recordings of spinal INs during a flexion/extension wrist task with an instructed delay period have shown directly that many spinal neurons modulate their rate during the preparatory period soon after a visual cue. The onset time and the relation between the delay period activity of spinal INs and the ensuing movement response suggest that this type of activity is not simply related to the forthcoming motor action, but rather reflects a correct match between the visual cue and the motor response. The existence of such activity further supports the notion that the motor system operates in a parallel mode of processing, so that even during early stages of motor processing multiple centers are activated regardless of their anatomical distance from muscles. The firing properties of spinal INs during the performance of the task seem to differ from the comparable properties of motor cortical cells. Spinal INs fire in a highly regular manner--their CV is substantially lower than the observed CV of cortical cells. Also, although neighboring cells tend to have similar response properties, the frequency of significant correlation is lower than for cortical cells and the anatomical extent of the correlation seems to be narrower. The similarity and differences between cortical and spinal cells in terms of response and firing properties suggests that while both type of cells are active in parallel throughout the behavioral phases of the motor task, each may operate in a different mode of information processing.

Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

OBJECTIVE: To determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS). METHOD: The probands of this study were 54 children with PANDAS (n = 24 with a primary diagnosis of OCD; n = 30 with a primary diagnosis of a tic disorder). One hundred fifty-seven first-degree relatives (100 parents [93%] and 57 siblings [100%]) were evaluated for the presence of a tic disorder. One hundred thirty-nine first-degree relatives (100 parents [93%] and 39 of 41 siblings over the age of 6 [95%]) were evaluated with clinical and structured psychiatric interviews to determine the presence of subclinical OCD, OCD, and other DSM-IV Axis I disorders. RESULTS: Twenty-one probands (39%) had at least one first-degree relative with a history of a motor or vocal tic; 6 mothers (11%), 9 fathers (19%), and 8 siblings (16%) received this diagnosis. Fourteen probands (26%) had at least one first-degree relative with OCD; 10 mothers (19%), 5 fathers (11%), and 2 siblings (5%), received this diagnosis. An additional 8 parents (8%) and 3 siblings (8%) met criteria for subclinical OCD. Eleven parents (11%) had obsessive-compulsive personality disorder. CONCLUSIONS: The rates of tic disorders and OCD in first-degree relatives of pediatric probands with PANDAS are higher than those reported in the general population and are similar to those reported previously for tic disorders and OCD. Further study is warranted to determine the nature of the relationship between genetic and environmental factors in PANDAS.

Sonographic demonstration of calculi within a urethral diverticulum.

A case in which sonography demonstrated that calculi may arise in female urethral diverticula is presented. The diagnosis of female urethral diverticula is reviewed.

In vivo tetracycline labeling of experimentally induced reparative dentin in human teeth.

Tetracycline hydrocholoride was administered to label reparative dentin in teeth indicated for extraction. Deep cavities or pulp capping performed on the teeth one of four months before extraction served as a stimulus for new dentin formation. Examination of undemineralized sections under ultraviolet light revealed fluorescent bands in the reparative dentin of most teeth. The technique can be safely used in studies of the effects of clinical procedures on the dentin and pulp of human teeth.

The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is a commonly performed procedure used in the evaluation of solitary thyroid nodules, in which the risk of malignancy is approximately 5% in most patients. Recently, the use of ultrasound (US) guidance in FNAB has been shown to enhance the diagnostic efficacy of this procedure. However, the risk of malignancy in thyroid nodules occurring within a multinodular goiter (MNG) has not been completely clarified, nor has the optimal means of investigating such nodules using FNAB. SUBJECTS AND METHODS: We performed a retrospective study of all patients seen over a 4-year period with a MNG that had one or more nodules who underwent FNAB under US guidance. The results from the history and physical examination, thyroid function and antibody tests, radionuclide studies, thyroid sonogram, cytology of aspirated nodules, and surgical pathology were recorded and analyzed. RESULTS: A total of 93 nodules were aspirated in 61 patients with MNG. Adequate material was obtained in 96% of aspirates on the first attempt. Sixty-seven aspirates in 44 patients yielded benign cytology and 22 aspirates in 15 patients yielded suspicious cytology. All patients with suspicious cytology underwent thyroid surgery. Thyroid cancer was found in 5 of these nodules, including 4 cases of papillary cancer and 1 case of Hürthle cell cancer, and 1 additional patient had occult papillary cancer discovered. The overall malignancy rate in thyroid nodules among the patients with MNG was approximately 5%. CONCLUSIONS: FNAB under US guidance is a useful diagnostic modality in the evaluation of thyroid nodules in selected patients with MNG. Because the risk of thyroid malignancy in these nodules is comparable to that which exists in solitary thyroid nodules, the possibility of thyroid malignancy should be considered in all patients with MNG.

Laryngeal radiation after hemilaryngectomy.

Laryngeal radiation was administered to 30 patients after hemilaryngectomy for true vocal cord carcinoma at Washington University Medical Center during the years 1957-1976. Twelve patients were irradiated at the time of gross recurrence and 5/12 (42%) of these patients had recurrence of their disease after radiation. Eighteen patients were irradiated immediately after hemilaryngectomy because positive margins were seen in the hemilaryngectomy specimen and 5/18 (28%) of these had recurrence. All but 1 recurrence occurred within 13 months following radiation. Total laryngectomy salvaged an additional 3 patients for ultimate cancer control in 23/30 (77%). This high dose laryngeal irradiation was well tolerated. A major complication occurred in 1 patient (3%) and consisted of permanent laryngeal edema necessitating tracheostomy but permitting useful speech. Mild complications occurred in 5 patients.

Tube feeding-related diarrhea in acutely Ill patients.

Acutely ill patients received tube feeding for an average of 15.8 days and, on average, 35% of those days were spent in the intensive care unit (ICU). Patients were prospectively assigned either a fiber-free formula (FFF-OSMOLITE HN, Ross; n = 50) or a fiber-supplemented (soy polysaccharide 14.4 g/L) formula (FSF = JEVITY, Ross; n = 50). Diarrhea was defined as three or more loose or watery stools per day and occurred in 30% of all patients. Diarrhea developed in 29 (41%) of the 71 patients who received antibiotics during, or within 2 weeks prior to, the feeding period, whereas only 1 (3%) of the 29 patients not receiving antibiotics developed diarrhea (p less than 0.005); and this patient developed diarrhea on the day of death. Among the 30 patients with diarrhea, stool Clostridium difficile (CD) toxin was positive in 15 (50%), negative in 11 (37%), and was not measured in four. The mean serum albumin was significantly lower in patients with diarrhea (2.43) than in those without diarrhea (2.75) (p = 0.043). There were no significant differences in age, sex, diagnoses, number of feeding days, and percent ICU days between patients with and without diarrhea. While not statistically significant, patients who received FSF were observed to have a lower incidence of diarrhea, a lower percentage of diarrhea days per total feeding days, and a lower frequency of positive CD toxin assays than patients who received FFF. In this patient population, antibiotic usage was the factor most strongly associated with diarrhea during tube feedings.

Repigmentation of the gingiva following surgical injury.

Oral melanin pigmentation is not uncommon in some races and ethnic groups. Repigmentation of depigmented oral mucosa has been described after chemical, thermal, surgical, pharmacologic or idiopathic factors. Information on the repigmentation of oral tissues after surgical procedures is extremely limited. The communication reports on gingival repigmentation over a 7 to 8 year period following removal of gingival tissues. Pigmented keratinized gingiva was removed in two Jewish Yemanite adult males, who had moderate or heavily pigmented gingiva. After surgery, the exposed lamina propria was covered by periodontal pack for 7 to 10 days. The tissues were then observed periodically for signs of repigmentation. Healing was uneventful and the surgically treated areas in both patients remained depigmented over the first 2 years. After 32 months, some pigmentation was found in one of the patients, and with the exception of two limited sites, the area was completely repigmented after 7 years. The surgically treated area in the second patient remained depigmented over an 8-year follow-up period. These observations agree with previous reports that describe gingival pigmentation as spontaneous and suggest that further controlled experimental studies be undertaken to explore the biologic basis for repigmentation.

Epignathus with placental hydrops.

A stillborn male infant with massive epignathus showed placental enlargement, hydramnios, and hydrops. These changes are thought to be due to cardiac decompensation from circulation of the large vascular tumor mass. Y bodies present in the tumor suggest a mitotic origin for epignathi from host cells.

Effects of high-frequency (500-600 Hz), antidromic stimulation on primary and secondary spindle afferents.

The aftereffects of antidromic stimulation at 500 or 600 Hz on the discharge of isolated spindle Ia and II, and tendon organ Ib afferent fibers from the cat medial gastrocnemius muscle were examined to see what proprioceptive disturbances to expect when such "high-frequency," tension-attenuating stimulation is used to modulate contractions in orthotic applications. Three phases of poststimulation depression in spindle discharge were recognized: a complete pause in firing, a rapidly accelerating return of discharge, and a final more gradual approach to the control rate. When steady prestimulation discharge rates of Ia and II endings were equated through adjustment of muscle length, no obvious difference in effect on duration of the pause or position sensitivity was detected. Sensitivity to dynamic change in muscle length was also depressed, but responses returned earlier than when the muscle was held at a steady length. The dynamic responses of tendon organs were similarly depressed.

Bayes risk weighted vector quantization with posterior estimation for image compression and classification.

Classification and compression play important roles in communicating digital information. Their combination is useful in many applications, including the detection of abnormalities in compressed medical images. In view of the similarities of compression and low-level classification, it is not surprising that there are many similar methods for their design. Because some of these methods are useful for designing vector quantizers, it seems natural that vector quantization (VQ) is explored for the combined goal. We investigate several VQ-based algorithms that seek to minimize both the distortion of compressed images and errors in classifying their pixel blocks. These algorithms are investigated with both full search and tree-structured codes. We emphasize a nonparametric technique that minimizes both error measures simultaneously by incorporating a Bayes risk component into the distortion measure used for the design and encoding. We introduce a tree-structured posterior estimator to produce the class posterior probabilities required for the Bayes risk computation in this design. For two different image sources, we demonstrate that this system provides superior classification while maintaining compression close or superior to that of several other VQ-based designs, including Kohonen's (1992) "learning vector quantizer" and a sequential quantizer/classifier design.

Banana flakes control diarrhea in enterally fed patients.

Diarrhea occurs frequently in the critically ill tube-fed population and may result from a multitude of causes. Despite the availability of antidiarrheal medications, diarrhea associated with enteral feedings remains a problem for clinicians and for the patients affected by it. We tested the hypothesis that administration of banana flakes would control diarrhea in critically ill patients receiving enteral feedings. Thirty-one patients with diarrhea and receiving enteral feedings were randomized to receive either banana flakes or medical treatment for diarrhea. Medical treatments included the use of pharmacological agents according to the discretion of the patient's physician or reducing feeding rates. Both banana flakes and medical treatments reduced the severity of diarrhea in critically ill tube-fed patients. Over the course of treatment, mean diarrhea scores were 21.64 +/- 7.81 for the banana flake group and 25.41 +/- 9.76 for the medical group. These differences were not statistically significant. Both groups achieved similar levels of nutrition support. The banana flake group had less diarrhea clinically, with 57% of the subjects diarrhea free on their last study day as opposed to 24% of the medically treated subjects. This occurred despite a threefold increase in the number of patients testing positive for Clostridium difficile toxin in the banana flake group. We conclude that banana flakes can be used as a safe, cost-effective treatment for diarrhea in critically ill tube-fed patients. Banana flakes can be given concurrently with a workup for C. difficile colitis, thereby expediting treatment of diarrhea.

Postinfectious and other forms of obsessive-compulsive disorder.

The search for subtypes of OCD has led to increased appreciation of the importance of distinguishing early (prepubertal) versus later on-set, and of tic-related versus non-tic related subtypes, as well as postinfectious forms of the disorder. How these apparent typologies relate to each other remains to be elucidated. Careful longitudinal clinical descriptive studies, as well as the ongoing application of genetic, neuroimaging, and immunologic techniques, promise to advance our understanding of how genotype and environmental factors interact to produce the diverse clinical forms of OCD and to point the way to more effective treatment.