Evidence for effectiveness of botulinum toxin for hyperhidrosis

Summary Hyperhidrosis refers to excessive and uncontrollable sweating beyond that is required to return body temperature to normal. Although a broad spectrum of treatment modalities are available including topical and systemic therapies, iontophoresis, and surgical interventions, their efficacy are usually short-term or are associated with unacceptable side effects. Recently, chemodenervation using botulinum toxin has emerged as a safe and effective treatment for both primary palmar and axillary hyperhidrosis in several clinical trials. In this article, we utilized the scale developed by the Therapeutics and Technology Assessment (TTA) subcommittee of the American Academy of Neurology evaluating current evidence supporting the use of botulinum toxin for the treatment of primary focal hyperhidrosis. As a result, there is a strong evidence to support the efficacy of botulinum toxin type A in axillary (Level A evidence) and palmar (Level B evidence) hyperhidrosis. Correspondence: Roongroj Bhidayasiri, MRCP (UK), Chulalongkorn Comprehensive Movement Disorders Center, Division of Neurology, Chulalongkorn University Hospital, Bangkok 10330, Thailand     

Evidence for the effectiveness of botulinum toxin for sialorrhoea

Summary Sialorrhoea is a common symptom in many neurological disorders. Recently, botulinum toxin has been introduced as a treatment for sialorrhoea, and in this paper, we review the evidence for its effectiveness. The publications on the topic were searched and reviewed independently by two authors using the scale developed by the Therapeutics and Technology Assessment subcommittee for the American Academy of Neurology. All papers identified in our search fulfilled were evaluated, and classified into 1 of the 4 levels of evidence. According to this scheme, the effectiveness of botulinum toxin A in the treatment of sialorrhoea is considered established (level A). Botulinum toxin B is considered probably effective in the treatment of sialorrhoea (level B). Correspondence: Daniel D. Truong, The Parkinson’s and Movement Disorder Institute, 9940 Talbert Ave., Fountain Valley, CA 92708, USA     

Strategies for the Development of Drugs for Pharmacoresistant Epilepsies

Summary: Presently, most strategies for development of antiepileptic drugs (AEDs) center around seizure models that are known to respond to presently marketed AEDs. These strategies do not take into account that epilepsy can be a progressive disease. Moreover, region-specific aspects of ep-ileptogenesis are rarely considered when new AEDs are developed. Seizures in the temporal lobe are often difficult to treat. Animal studies on various seizure models in the hippocampus and the entorhinal cortex (EC) suggest that these structures do not a priori produce seizures that are difficult to treat. However, seizure-like events in the EC tend to progress to a state of status epilepticus-like activity that cannot be suppressed by presently marketed AEDs. Loss of 7-aminobutyric acid (GABA)ergic neurotransmission and increased excitatory synaptic coupling seem to cooperate for induction of this state. Epilepsy induced alterations in the interaction between the EC and the hippocampus may lead to alterations that facilitate precipitation of seizures. Because of the recurrent interaction between the hippocampus and the EC, these seizures may reach an intensity that is no longer controllable by presently available AEDs. Ontogenetic alterations of the circuitry between the EC and the hippocampus. seizure-induced stabilization of synaptic connections over-expressed during ontogenesis, seizure-induced lesions and subsequent rearrangements of internal cell properties, and synaptic arrangements and kindling-like alterations of nerve cell and glial behavior may all be involved in the generation of a neuronal aggregate whose balance between inhibitory and excitatory processes becomes readily disturbed. Strategies for the development of AEDs treating such seizures should suppress hyperactivity and prevent progression of epilepto-genesis. AEDs directed against seizures may be effective if they can be given in sufficient concentrations to suppress very intense local seizures.     

Searching for new targets for treatment of pediatric epilepsy

The highest incidence of seizures in humans occurs during the first year of life. The high susceptibility to seizures in neonates and infants is paralleled by animal studies showing a high propensity to seizures during early life. The immature brain is highly susceptible to seizures because of an imbalance of excitation and inhibition. While the primary outcome determinant of early-life seizures is etiology, there is evidence that seizures which are frequent or prolonged can result in long-term adverse consequences, and there is a consensus that recurrent early-life seizures should be treated. Unfortunately, seizures in many neonates and children remain refractory to therapy. There is therefore a pressing need for new seizure drugs as well as antiepileptic targets in children. In this review, we focus on mechanisms of early-life seizures, such as hypoxia–ischemia, and novel molecular targets, including the hyperpolarization-activated cyclic nucleotide-gated channels. This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Considerations for Intentional Use of Self-Disclosure for Family Therapists

One of the most debated ethical issues in psychotherapy is that of therapist self-disclosure. In this article, relevant marriage and family therapy literature on therapist self-disclosure will be presented. The influence of practice setting, particularly in training clinics and private practice, on therapist self-disclosure is discussed. A distinction is drawn between intentional and spontaneous self-disclosure. Risks for excessive self-disclosure become amplified in private practice, whereas training clinics are more likely to discourage the use of self-disclosure as a clinical technique. Literature presented is intended to demonstrate that advanced training settings and advanced practice settings hold disparate positions on the issue of self-disclosure. This gap between advanced training and advanced practice may leave therapists open to ethical vulnerabilities. Recommended steps toward intentional and ethical practice are presented.     

Early recognition of heterozygotes for the gene for dystrophia myotonica

A study has been performed on 124 first degree relatives of 38 index patients with dystrophia myotonica in order to assess means of detecting heterozygotes before neurological complaints. Some or all of the following tests have been performed on the relatives: clinical examination, electromyography, slit-lamp examination, radiography of the skull, electrocardiography, serum insulin, and serum immunoglobulin levels. There is evidence that abnormalities in symptomless heterozygotes may be detected by slit-lamp examination, electromyography, and immunoglobulin concentration, and this is probably the order of usefulness of the test in early recognition of the disease. In this study 13 previously undetected heterozygotes have been identified: six as a result of neurological examination, four by both electromyography and slit-lamp examination, and three by slit-lamp examination alone. Abnormalities detected by these tests appear to be independently manifest, so that they will probably be more useful in combination than singly. The family data give a maximum estimate for incidence of mutations among index cases of one quarter, lower than previously suggested. The estimation of immunoglobulins in 45 patients showed significant deficiency, as compared with controls, not only of IgG but also of IgM, and there was an insignificant trend for IgA to be low too. This suggests that the abnormally rapid catabolism of immunoglobulin, previously reported, is not specific for IgG.     

Ink-jet printing for micropattern generation of laminin for neuronal adhesion

In order to achieve defined adhesion and neurite outgrowth, the growth substrate must be patterned in an appropriate way. We utilised ink-jet printing by means of a piezo-based microdispenser to create defined line patterns of a polymer with typical dimensions of 100 microm width on glass, silicon, gold and carbon substrates. Vinnapas, a co-polymer of vinyl acetate and ethylene, was mixed with the extracellular matrix protein laminin to achieve neuronal adhesion on the surface of the patterns. It could be demonstrated that the laminin entrapped in the polymer lines can be recognised by a specific antibody. Adhesion of embryonic chicken forebrain neurones is following the prepared lines, and identity of adhering cells could be shown by neurofilament staining. These findings open the route for the generation of complex small neuronal arrays and for the electrochemical investigation of the obtained neuronal matrix.     

Traits for selection of paraprofessionals for behavior-modification consultation training

This paper aims at specifying the characteristics associated with success in behavior-modification consultation. Consultants were undergraduate paraprofessionals who completed a program in consultation. Discussed are the training procedures, the psychometric and other selection measures, and statistical results when comparing the selection tools with different criteria.     

Evaluating requirements for spatial resolution of fMRI for neurosurgical planning

The unambiguous localization of eloquent functional areas is necessary to decrease the neurological morbidity of neurosurgical procedures. We explored the minimum spatial resolution requirements for functional magnetic resonance imaging (fMRI) data acquisition when brain mapping is used in neurosurgical planning and navigation. Using a 1.5 Tesla clinical MRI scanner, eight patients with brain tumors underwent fMRI scans using spatial resolution of approximately 4 x 4 x 4 mm(3) to map the eloquent motor and language areas during the performance of cognitive/sensorimotor tasks. The fMRI results were then used intra-operatively in an open MRI system to delineate eloquent areas. Retrospectively, activation patterns were visually inspected by a neurosurgeon to determine qualitatively whether ambiguity with respect to the activation boundaries, due to low spatial resolution, could be of potential significance for surgical guidance. A significant degree of ambiguity in both the extent and shape of activation was judged to be present in data from six of the eight patients. Analysis of fMRI data at multiple resolutions from a normal volunteer showed that at 3 mm isotropic resolution, eloquent areas were better localized within the gray matter although there was still some potential for ambiguity caused by activations appearing to cross a sulcus. The data acquired with 2-mm isotropic voxels significantly enhanced the spatial localization of activation to within the gray matter. Thus, isotropic spatial resolution on the order of 2 x 2 x 2 mm(3), which is much higher than the resolutions used in typical fMRI examinations, may be needed for the unambiguous identification of cortical activation with respect to tumors and important anatomical landmarks.     

Personality predictors of outcome for adolescents hospitalized for suicidal ideation

OBJECTIVE: Recent cross-sectional studies of adolescents have noted an association between the personality traits of perfectionism and self-criticism and suicidal ideation. The present study was undertaken to examine the relationship between personality dimensions and the outcome of treatment of adolescents hospitalized for suicidal ideation or behavior. METHOD: The study group was composed of 78 adolescents who were admitted to an adolescent psychiatric inpatient unit for suicidal ideation or attempts. Subjects completed measures of self-criticism, interpersonal dependency, self-oriented perfectionism, and socially prescribed perfectionism as well as the broad, higher-order trait neuroticism. Depression symptoms, hopelessness, and suicidal ideation were assessed at the beginning (time 1) and end (time 2) of their inpatient treatment. Readmissions were identified by review of medical records 1 year after hospital discharge. RESULTS: After controlling for baseline symptoms, neuroticism was associated with posttreatment depression and suicidal ideation. After controlling for time 1 symptoms and neuroticism in multiple regression analyses, self-criticism was associated with post-treatment hopelessness and depression. Logistic regression analysis was used to identify predictors of readmission. Baseline suicidal ideation and neuroticism were predictive of psychiatric readmission within 1 year of discharge. CONCLUSIONS: Neuroticism and self-criticism are potentially useful predictors of outcome in suicidal adolescents and can be assessed quickly and reliably. Therapeutic interventions directed at self-criticism (e.g., cognitive-behavioral therapy) may be useful in the treatment of suicidal adolescents.     

Use of conivaptan for management of hyponatremia following surgery for Cushing's disease

Background

Hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common osmoregulatory complication following surgery for Cushing's disease. Conventional management includes water restriction and sodium repletion, however this regimen does not address the underlying pathophysiology of excessive vasopressin production. Vaptans are arginine vasopressin receptor antagonists shown to be effective in correcting water excess in other disease states of euvolemic and hypervolemic hyponatremia. The use of these agents has not been reported in Cushing's patients.

Methods

We retrospectively studied Cushing's patients at our institution with post-surgical hyponatremia (Na < 130 mEq/L) treated with and without conivaptan between 2005 and 2011. We report rates of serum sodium normalization and compare length-of-stay (LOS) between the groups.

Results

Hyponatremia developed in six of 98 patients (6.1%) undergoing resection of ACTH-positive pituitary adenomas. Three patients received conivaptan and fluid restriction ± sodium supplementation, and three received conventional therapy alone. The rate of serum sodium normalization with conivaptan was 5.8 ± 2.3 mEq/L/20 mg IV bolus given every 24 h. All patients receiving conivaptan were discharged with normal serum sodium values and no instances of rapid overcorrection occurred. A trend toward longer LOS occurred in patients treated with conivaptan (4.6 ± 0.3 days, mean ± SE) versus conventional therapy alone (1.6 ± 0.3 days).

Conclusions

Conivaptan is a potentially useful treatment option for hyponatremia in the setting of Cushing's disease patients after pituitary surgery.     

Long-term follow-up of DBS of thalamus for tremor and STN for Parkinson's disease

In 1994 we commenced deep brain stimulation (DBS) of the thalamus for patients with severe tremor. This was done under the guidance of Professor Alim Benabid from Grenoble, France, who pioneered the technique. In the beginning we commenced DBS of the thalamus for patients with severe tremulous Parkinson's disease, essential tremor, and in one case, severe post-traumatic tremor. In all, we had 28 patients for whom the procedure was performed for tremulous Parkinson's disease, six patients with essential tremor and one patient with post-traumatic tremor. In 1997, again under the guidance of Professor Benabid, we commenced bilateral subthalamic nucleus stimulation (STN) for patients with severe Parkinson's disease. We were the second unit in Australia to become established for these procedures. A total of 45 patients have undergone STN DBS and have been followed up on a regular basis by the same neurologist (DOS). The surgical complications and long-term complications, including hardware problems will be reviewed retrospectively, as well as the long-term benefits of these surgical procedures.     

Process measures for the assessment and improvement of quality of care for schizophrenia

The development of process measures for the assessment and improvement of care for schizophrenia is at an early stage. As part of a national inventory of mental health quality measures, we identified 42 process measures developed to assess the quality of schizophrenia care. A greater proportion of measures assessed pharmacotherapy than assessed psychosocial interventions or other clinical processes, such as assessment, continuity, or coordination. Twenty-five measures (60%) were based on research evidence linking measure conformance with improved patient outcomes, while 17 (40%) were based on clinical consensus or opinion. Only 12 measures (29%) were fully operationalized. Few were tested for validity or reliability. A number of demonstration projects currently under way should expand the pool of well-developed and tested measures. Further research and consensus development will be needed to identify common measurement priorities, reduce the data collection burden, enhance the interpretability of results, and allow for comparisons of clinical practice across facilities and health care systems.     

Novel substrates for, and sources of, progestogens for reproduction

Steroid hormones, such as progesterone, are typically considered to be primarily secreted by the gonads (albeit adrenals can also be a source) and to exert their actions through cognate intracellular progestin receptors (PRs). Through its actions in the midbrain ventral tegmental Area (VTA), progesterone mediates appetitive (exploratory, anxiety, social approach) and consummatory (social, sexual) aspects of rodents' mating behaviour. However, progesterone and its natural metabolites ('progestogens') are produced in the midbrain VTA independent of peripheral sources and midbrain VTA of adult rodents is devoid of intracellular PRs. One approach that we have used to understand the effects of progesterone and mechanisms in the VTA for mating is to manipulate the actions of progesterone in the VTA and to examine effects on lordosis (the posture female rodents assume for mating to occur). This review focuses on the effects and mechanisms of progestogens to influence reproduction and related processes. The actions of progesterone and its 5α-reduced metabolite and neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP; allopregnanolone) in the midbrain VTA to facilitate mating are described. The findings that 3α,5α-THP biosynthesis in the midbrain occurs with mating are discussed. Evidence for the actions of 3α,5α-THP in the midbrain VTA via nontraditional steroid targets is summarised. The broader relevance of these actions of 3α,5α-THP for aspects of reproduction, beyond lordosis, is summarised. Finally, the potential role of the pregnane xenobiotic receptor in mediating 3α,5α-THP biosynthesis in the midbrain is introduced.     

A simulator for evaluating methods for the detection of lesion-deficit associations

Although much has been learned about the functional organization of the human brain through lesion-deficit analysis, the variety of statistical and image-processing methods developed for this purpose precludes a closed-form analysis of the statistical power of these systems. Therefore, we developed a lesion-deficit simulator (LDS), which generates artificial subjects, each of which consists of a set of functional deficits, and a brain image with lesions; the deficits and lesions conform to predefined distributions. We used probability distributions to model the number, sizes, and spatial distribution of lesions, to model the structure-function associations, and to model registration error. We used the LDS to evaluate, as examples, the effects of the complexities and strengths of lesion-deficit associations, and of registration error, on the power of lesion-deficit analysis. We measured the numbers of recovered associations from these simulated data, as a function of the number of subjects analyzed, the strengths and number of associations in the statistical model, the number of structures associated with a particular function, and the prior probabilities of structures being abnormal. The number of subjects required to recover the simulated lesion-deficit associations was found to have an inverse relationship to the strength of associations, and to the smallest probability in the structure-function model. The number of structures associated with a particular function (i.e., the complexity of associations) had a much greater effect on the performance of the analysis method than did the total number of associations. We also found that registration error of 5 mm or less reduces the number of associations discovered by approximately 13% compared to perfect registration. The LDS provides a flexible framework for evaluating many aspects of lesion-deficit analysis.     

Proposal for a new five-axis classification scheme for psychoses of epilepsy

Based on an overview of the literature and a multicenter study in Japan, we propose a new five-axis classification scheme for psychoses of epilepsy: (1) epilepsy variables, (2) psychopathology variables, (3) ictus/EEG variables, (4) precipitating factors of psychoses, (5) organic background. A total of 128 patients, 63 males and 65 females, with epilepsy and psychoses were recruited from five treatment centers. A wide heterogeneity of psychoses of epilepsy was demonstrated and categorization by a single axis was shown to be inadequate. Cluster analysis revealed four subgroups characterized by their psychopathology, temporal relationship to seizure occurrence, and EEG changes during psychoses. By comparing with the control epileptic group without psychoses, higher rates of mild intelligence disturbance and abnormal findings by brain imaging were proven among the psychotic group. The scheme involves a dimensional representation of individual patients to capture the complexity of their clinical background and to relay clinical information accurately and systematically. It is believed to hold direct therapeutic implications and to contribute to promoting research by enabling accumulation of a large number of patients on a multicenter basis.     

A modified technique for syringo-subarachnoid shunt for treatment of syringomyelia.

Syringo-subarachnoid shunting is a well-established procedure for the treatment of syringomyelia. However, the standard surgical procedure requires a laminectomy and posterior midline myelotomy, which have potential complications. In this study, we describe our clinical experience with a modified technique for syringo-subarachnoid shunt insertion in eight patients between 1998 and 2002. The technique comprises a limited hemilaminectomy, a 2 mm myelotomy at the site of dorsal root entry zone, introduction of a 1.5 mm thick catheter into the syrinx and placement of the distal tip of the catheter in the anterolateral subarachnoid space. Using this technique there was no operative morbidity or mortality. Collapse of the syrinx, in the first post-operative month, was demonstrated by MRI in all cases. There were no relapses in the follow-up period. Although our experience is limited and the results preliminary, this technique is less invasive than commonly used techniques and the results are favorable.     

A New Method for Fixation of Probes for Transcranial Doppler Ultrasound

Although monitoring of blood velocity in the cerebral arteries with transcranial Doppler ultrasound is standard practice, methods for fixation of the ultrasound probe to the skull continue to impose a technical challenge. This report describes a novel method of probe fixation in which an inexpensive polymer block is custom–made for each patient to hold the probe at a fixed angle. In addition to comfort and durability, its major advantage is that the polymer block prevents dislodgment of the probe from the intended angle by forces of gravity or by patient movement. Thirty–one temporal windows were monitored with this technique, with stable signals obtained in all subjects despite aggressive movements. Disadvantages include the inability to insonate more than one vessel and the cost for each block. However, the method is quick, is relatively inexpensive, and provides significant advantages of probe stability.