Meta-analysis of vagus nerve stimulation treatment for epilepsy: correlation between device setting parameters and acute response.

BACKGROUND: Vagus nerve stimulation (VNS) is an adjunctive neurophysiological treatment for those patients who have pharmacoresistant or surgically resistant partial onset epilepsy. OBJECTIVE: The aim of this study is to determine the effects of high and low stimulation paradigms on a responder rate of ≥50 and ≥75% reduction in seizure frequency and associated adverse effects in adults and children. METHOD: A literature search was performed using Medline, PubMed, EMBASE, and Cochrane library for studies using vagus nerve stimulation published from January 1980 until July 2014 for medically or surgically resistant partial onset seizures, in children and adults. No restrictions on languages were imposed. DATA COLLECTION AND ANALYSIS: Four authors reviewed and selected studies for inclusion and exclusion. The search identified five randomized control trials that fit with our inclusion criteria. The following outcomes were evaluated: 50% or greater reduction in total seizure frequency, 75% or greater reduction in total seizure frequency, and adverse effects. RESULTS: Four randomized controlled trials were analyzed in this meta-analysis. Results indicate high stimulation is more effective in adult patients who experienced ≥50 and ≥75% reduction in seizure frequency with a significant difference within both high and low stimulation groups. In children, there was no significant difference between the two groups and patients with ≥50 % reduction in seizures. Adverse effects such as hoarseness and dyspnea were more common in the high stimulation group where the remaining side effects were not statistically different among both groups. CONCLUSION: High stimulation is more effective than low stimulation in producing a greater reduction in seizure frequency in patients with medically and surgically resistant epilepsy.

Review: neuropathology of acute phase encephalitis lethargica: a review of cases from the epidemic period.

INTRODUCTION: Encephalitis lethargica (EL), an epidemic disease of the early 20th century, has continued to be diagnosed sporadically since that time, including a report of 20 new cases in 2004. Many of the recent case reports state that the primary neuropathology of acute EL consists of inflammatory changes and lesions within the midbrain, basal ganglia and substantia nigra. However, the neuropathology of acute EL cases from the epidemic period was actually much more widespread. METHODS: In order to characterize the neuropathology of acute phase EL, we developed a database of EL pathology based on 112 cases from the years 1915 to 1940, of which most died within 2 weeks of EL onset. RESULTS: Our analysis revealed that cortical damage was prevalent in 75% of the 112 cases; damage to the meninges and brainstem occurred in approximately half of the cases; and the substantia nigra was damaged in only 13% of these acute cases. We also found that after 1921, damage to cranial nerve nuclei was not reported. An analysis of the neuropathology and clinical symptoms revealed little correlation. CONCLUSIONS: Based on these findings, putative modern cases of acute EL with MRI/CT indicated lesions confined solely to the midbrain, brainstem, and/or basal ganglia should not be considered, consistent with that reported during epidemic period.

Vascular-targeted photodynamic therapy (VTP) of a canine-transmissible venereal tumour in a murine model with Pd-bacteriopheophorbide (WST09).

Abstract Treatment of canine-transmissible venereal tumour (CTVT) with local vascular-targeted photodynamic therapy (VTP) using Pd-bacteriopheophorbide (WST09) as a drug is suggested as an alternative to conventional chemotherapy. Male CD1 nude mice were subcutaneously grafted with the xenograft-transmissible canine venereal tumour (XTVT). The VTP protocol delivered once consisted of intravenous administration of WST09 (10 mg kg(-1)) followed by immediate local illumination with a diode laser (763 nm). Controls included animals treated with light or WST09 alone. Macroscopic and microscopic evaluations of tumour response were conducted 10, 24 and 48 h after treatment. Upon VTP, tumours underwent necrosis that lasted 8-10 days and exhibited complete healing by 25-35 days, reaching an overall long-term cure rate (83%) by 90 days after treatment. This study suggests that VTP with WST09 can efficiently treat CTVT in a single session, as compared with 4-6 sessions of chemotherapy and thus may be feasible for common veterinary practice, particularly under ambulatory conditions.

Sensory disturbances after focal extirpations of the human "motor" cortex.

From the late 1800s until approximately the middle of the 20th century, neurosurgeons made discrete motor cortex lesions in humans in attempts to reduce or eliminate a variety of involuntary movements, resulting mainly from epilepsy. In some cases, the neurosurgeons tested and recorded their patients' ability to perform various movements and to perceive various types of sensory stimuli after the operation. Although these studies have been largely forgotten, they have an immense advantage over primate lesion studies for understanding the function of the motor cortex because the patients were able to attempt to perform complex movements upon request, and to describe their perceptions of cutaneous stimuli, including integrated sensations (e.g., recognition of objects by palpation alone). We provide here a table containing the results of these studies pertaining to sensory deficits. The most consistent and persistent sensory deficits reported relate to object recognition and position sense. This finding is in keeping with recent electrophysiological studies in primates. Our analysis suggests that the "motor" cortex serves important sensory functions; hence, the term sensorimotor cortex, remains appropriate for the primate precentral (and postcentral) cortex.

Serratus posterior muscles: anatomy, clinical relevance, and function.

The serratus posterior superior and inferior muscles are generally considered clinically insignificant muscles that, based on attachments, probably function in respiration. Interestingly, however, there is no evidence supporting a respiratory role for these muscles. In fact, some electromyographic data refute a respiratory function for these muscles. We suggest that the serratus posterior muscles function primarily in proprioception. Further, these muscles, especially the superior, have been implicated in myofascial pain syndromes and therefore may have greater clinical relevance than commonly attributed to them.

Integrating the work of D. Denny-Brown and some of his contemporaries into current studies of the primate motor cortex.

Most contemporary investigators who study the behavioral effects of lesions of the primate motor cortex evaluate their findings in comparison to those of other recent investigators, but not in relation to the experimental neurologists who dominated this field around the mid-part of the 20th century. Utilizing selected recent reports, we demonstrate that these earlier papers, primarily those by D. Denny-Brown, provide valuable insights into the interpretation of some modern studies. Thus, we suggest that contemporary investigators of the primate motor cortex thoroughly review articles by the mid-20th century experimental neurologists. In addition, Denny-Brown and his contemporaries studied the effects of lesions in many other parts of the primate nervous system, and the associated reports are presumably also relevant to current investigations of these areas of the CNS.

Do quadrupeds require a change in trunk posture to walk backward?

Previous studies on cats walking backward have indicated that they adopt a presumably adaptive posture characterized by extreme dorsiflexion of the lumbar spine. Because humans do not show any marked postural changes during backward walking, we questioned whether the posture exhibited by cats during backward walking was in fact adaptive and whether it was typical of quadrupeds. We therefore compared forward and backward walking in three treadmill-trained dogs and found reduced temporal parameters during backward walking and a marked reduction in wrist palmar-flexion during the swing phase of a backward step, but no change in trunk posture. We suggest that the aberrant posture exhibited by cats during backward walking is more related to ethological factors than to biomechanical ones.

Sacroiliac joint innervation and pain.

The present paper reviews current knowledge on the innervation of the human sacroiliac joint (SIJ). We conclude, based on a recent anatomic study on adult cadavers, with fetal correlation, that the joint is predominantly, if not entirely, innervated by sacral dorsal rami. This conclusion is in agreement with patterns of referred pain reported by asymptomatic volunteers upon direct SIJ capsular stimulation and with a reduction in pain in patients treated for (presumptive) SIJ pain by injection of an anesthetic into the SIJ. We also present preliminary data suggesting that the periarticular tissues of the SIJ, like those of other synovial joints, contain mechanoreceptors and nociceptors that function to inform the central nervous system about the state of the joint.

Denny-Brown's views on the pathophysiology of dystonia.

We review Denny-Brown's hypotheses on the mechanisms underlying motor behavior and his views on how dysfunction in these mechanisms can result in dystonia. His formulations were based upon clinical observations of patients with diseases of the central nervous system and on monkeys with surgically-induced lesions of structures affected by diseases in his patients. Denny-Brown viewed dystonia as resulting from an imbalance of reflex responses to natural stimulation, both tonically and phasically. The evidence for this view came from demonstration of alterations of dystonic postures by natural vestibular, cutaneous, proprioceptive and visual stimuli. His formulations remain highly useful to clinicians faced with a bewildering variety of postural and movement disorders.

Disorders of proprioceptive responses in monkeys after cerebellar lesions: an analysis using the Denny-Brown Collection.

We used the Denny-Brown Research Collection to study in detail the reflex responses of monkeys after ablation of the anterior lobe, posterior lobe or the entire cerebellum. The Collection includes written, film and histological records, and photographs of the brain at autopsy. Large cerebellar ablations severely suppress proprioceptive responses, thereby significantly impairing the capacity to stand, walk, and hop. Cutaneous reflexes are also impaired, although more selectively, permitting expression of normally suppressed responses such as magnet reactions and tactile avoiding responses. Enhancement (release) of responses to truncal cutaneous stimulation, along with suppression of opposing proprioceptive responses, leads to postures of persistent flexion. Large cerebellar lesions also interfere with reflex responses mediated by visual and vestibular systems. More limited cerebellar ablations have similar, but less severe effects.

Stumbling corrective responses in healthy human subjects to rapid reversal of treadmill direction.

The kinematics of stumbling and recovery induced by a rapidly reversing treadmill is described for eight healthy adults. Stability was achieved in approximately 400 ms following treadmill reversal (initiated at heel-strike) and the ensuing stumble. It appeared to be accomplished primarily by rapid flexion of the thigh and knee of the stance limb, which prevented damage to the knee joint and lowered the trunk, and by extension of the contralateral joints (swing limb), which contacted the ground presumably to deliver an impulsive thrust to counter the backward lean of the trunk. The movements of the ankle also contributed to the recovery from the stumble, but its movements were markedly more variable among the subjects than those of the thigh and knee. The observed kinematics to some extent resembled a crossed-extension reflex, which may have been triggered by muscle, joint, cutaneous or vestibular afferents. These data should provide a baseline by which to compare groups in which recovery from stumbling is known to be deficient (e.g., the elderly).

'Mouth-feeding' in monkeys after sensorimotor system lesions: an analysis based upon the Denny-Brown collection.

Utilizing the Denny-Brown collection, we investigated an unusual feeding behavior exhibited by monkeys after sequential pre- and post-central gyrus lesions. The behavior involves ingestion of food by placing the lips directly over the food object, i.e., 'mouth-feeding.' Interestingly, this behavior persists long after recovery of the ability to hand-feed. In all of the cases within the collection and in descriptions of mouth-feeding found in the literature, mouth-feeding occurs only after bilateral lesions. We suggest that the co-existence of mouth- and hand-feeding behavior in animals with pre- and post-central gyrus lesions results partly from the sparing of corticospinal projections arising outside these gyri, e.g., the cingulate region, thereby preserving to a certain extent discrete use of the forelimbs.

Neurogenic acceleration of osteoarthritis.

The nervous system has a variety of mechanisms whereby it can potentially initiate or accelerate joint disease. Whether these potential mechanisms are clinically significant factors in the etiology of osteoarthritis remains uncertain. However, 11 papers published in the past year provide further support for the view that these mechanisms are important in the pathogenesis of the disease.

Positive and negative factors in movement control: a current review of Denny-Brown's hypothesis.

In his extensive writings, Denny-Brown hypothesized that two competitive 'tropisms,' one positive (exploratory) and one negative (withdrawal) act to coordinate normal movements at all levels of the neuraxis. Lesions in particular areas of the central nervous system result in disequilibrium between these tropisms, leading to disorders of posture and movement, including involuntary movements. The tactile manifestations of unbalanced exploratory tropisms are grasping responses, whereas the complementary withdrawal tropisms are avoiding responses. In Denny-Brown's view, at the level of the cerebral cortex, grasping responses result from frontal lobe injury whereas avoiding responses result from parietal lobe lesions. In this report we review Denny-Brown's conceptions of positive and negative tropisms, their anatomical loci, and whether his hypothesis has merit in a contemporary approach to brain function. We find that Denny-Brown's view on the anatomical loci associated with these behaviors is incomplete, but that the idea of conflicting behavioral tendencies is valuable for understanding and managing some neurological and perhaps also psychiatric disorders. For example, his hypothesis offers an important perspective in understanding the paradoxical success of stereotaxic surgery to alleviate the symptoms of Parkinson's disease.

Serial kinematic analysis of the canine hindlimb joints after deafferentation and anterior cruciate ligament transection.

OBJECTIVE AND DESIGN: Transection of the anterior cruciate ligament 2 weeks after ipsilateral hindlimb deafferentation leads to osteoarthritis of the knee joint within 3 weeks. We analyzed the gait of six dogs that underwent this procedure in order to identify kinematic changes that could account for this rapid joint degeneration. All animals were video taped, 1, 3, 6, 9 and 13 weeks after surgery while they trotted on a treadmill. RESULTS: In each dog, extension of the hip, knee and ankle joints of the unstable limb was increased, and the yield phase of the unstable knee was delayed or attenuated. When killed, five of six dogs showed a large full-thickness cartilage ulcer on the distal and/or anterior surface of the medial femoral condyle of the unstable knee; in the sixth dog, a smaller ulcer was observed. However, the severity of pathology in each individual was not obviously related to difference among the dogs in postoperative joint kinematics. CONCLUSIONS: These data, and results of prior studies in humans and dogs, suggest that knee hyperextension resulting from limb deafferentation, and knee instability resulting from anterior cruciate ligament transection, operate in concert to create a mechanical environment (i.e., increased tibiofemoral separation and changes in the loading of articular surfaces) that results in rapid joint breakdown.

Utilization of the Denny-Brown collection: differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions.

The Denny-Brown collection of primate lesion material was used to test the hypothesis that there is a difference in the rate of forelimb and hind limb recovery of locomotor movements after major unilateral cerebral ablation (pre/postcentral gyrus, decortication or hemispherectomy). The results indicate that, following major cerebral injury, hind limb recovery precedes that of the forelimb in adolescent and adult primates, but not in infants. This suggests that there is an underlying physiological basis to the widely-held belief that, in humans, lower limb recovery after stroke is generally more complete than that of the upper limb.