Late Paralysis Research Articles

Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity

Indications for vagus nerve stimulation (VNS) therapy include focal, multifocal epilepsy, drop attacks (tonic/atonic seizures), Lennox-Gastaut syndrome, tuberous sclerosis complex (TSC)-related multifocal epilepsy, and unsuccessful resective surgery. Surgical outcome is about 50-60% for seizures control, and may also improve mood, cognition, and memory. On this basis, VNS has also been proposed for the treatment of major depression and Alzheimer's' disease. The vagus nerve stimulator must be implanted with blunt technique on the left side to avoid cardiac side effects through the classic approach for anterior cervical discectomy. The actual device is composed of a wire with three helical contacts (two active contacts, one anchoring) and a one-pin battery. VNS is usually started 2 weeks after implantation with recommended settings of stimulation (1.0-2.0mA; 500μs pulse width; 20-30Hz; 30s ON, 5min OFF). The complications of VNS therapy are early (related to surgery) and late (related to the device and to stimulation of the vagus nerve). Early complications include the following: intraoperative bradycardia and asystole during lead impedance testing, peritracheal hematoma, infections (3-8%), and vagus nerve injury followed by hoarseness, dyspnea, and dysphagia because of left vocal cord paralysis. Delayed morbidity due to the device includes late infections or problems in wound healing; other more rare events are due to late injury of the nerve. Late complications due to nerve stimulation include delayed arrhythmias, laryngopharyngeal dysfunction (hoarseness, dyspnea, and coughing), obstructive sleep apnea, stimulation of phrenic nerve, tonsillar pain mimicking glossopharyngeal neuralgia, and vocal cord damage during prolonged endotracheal intubation. The laryngopharyngeal dysfunction occurs in about 66% of patients and is usually transitory and due to the stimulation of the inferior (recurrent) laryngeal nerve. A true late paralysis of the left vocal cord is often partial and rare (1-2.7%), and usually transitory, and may be caused by previous surgical trauma (i.e., damage of nerve fibers and/or of their blood supply) or to a supposed chronic denervation during stimulation. Surgery for complete removal or revision and replacement of the device is to be considered in cases of device malfunction (4-16.8%), failure of VNS therapy, intolerable side effects, or because of patient's specific request. As described in the literature, the surgical techniques of lead revision and replacement are two: sharp and blunt dissection of helical electrodes and replacement; and blunt dissection combined with ultrasharp low-voltage cautery dissection. The incidence of left vocal cord palsy after vagus nerve stimulator replacement/revision is slightly higher than that of first implantation (4.9% vs. 3.8%). A de novo implantation in a naive segment of the left or right vagus nerve may be considered in specific cases; the use of the right vagus nerve is a rare exception that may be chosen with an acceptable result.

Residual anaesthesia drugs in intravenous lines – a silent threat?

Residual anaesthesia drugs in intravenous lines – a silent threat?

Four Distinct Neurologic Syndromes in Marek's Disease: Effect of Viral Strain and Pathotype

A chronological study of central nervous system disorders induced by Marek's disease virus (MDV) has been conducted. Neurologic clinical signs were recorded daily for individual chickens of two genetic lines after inoculation of 13 serotype 1 MDV strains representing all three pathotypes. In addition to classical transient paralysis (TP) previously described by many workers, and acute TP, described in the companion paper, we have identified for the first time two other neurologic syndromes, persistent neurologic disease (PND) and late paralysis (LP). PND designates birds that showed a variety of neurologic signs (ataxia, torticollis, and nervous tics) after recovery from paralysis (12-15 days postin-oculation [DPI]) that either persisted through the observation period or presented a cyclic pattern. LP was a rare syndrome characterized by the late onset of the paralytic stage (about 20 DPI), perhaps indicating occasional failure of the initial intraabdominal inoculation to induce infection. Clinical signs and histopathologic alterations of the brain were also evaluated sequentially in chickens of two genetic lines after inoculation with two MDV strains (virulent MDV and very virulent plus MDV). Although clinical response differed greatly among treatment groups, types of lesions (endotheliosis, mononuclear perivascular cuffing, vasculitis, vacuolization, and increase in cellularity of the neuropil) were similar. However, early onset of lesions (by 6 days) appeared to be associated with a greater severity of clinical signs. We also found that neurologic response was greatly influenced by viral pathotype (virulence). This study thus confirms that the central nervous system is an important target organ for MDV resulting in several distinct clinical manifestations and suggests that neurologic responses in antibody-free chickens might be a useful criterion for virus pathotyping.

Enhancement by hyperthermia of the 'early delayed' and 'late delayed' radiation response of the rat cervical spinal cord.

The cervical spinal cord (C5-T5) of female Wistar WU rats was irradiated with 250 kV X-rays (15-32 Gy). Heat was applied at approximately the same site 7 +/- 1 min after X-rays. 'Early delayed' paralysis of the forelegs was observed 5-10 months after treatment. The ED50 (+/- SE) after single-dose irradiation alone was 25.8 +/- 0.4 Gy. 'Late delayed' paralysis and paresis were observed 11-21 months after irradiation with an ED50 (X-rays alone) of 22.7 +/- 0.6 Gy. The data for late paralysis, late paresis and minor neurological symptoms were pooled resulting in an ED50 (+/- SE) of 20.6 +/- 0.7 Gy. Hyperthermia enhanced the radiation response. Thermal enhancement ratios (TER) in the 'early delayed' response after a 30 min treatment with 41.1 +/- 0.4 degrees C 42.1 +/- 0.4 degrees C and 42.9 +/- 0.4 degrees C were 1.07 +/- 0.08, 1.17 +/- 0.08 and 1.12 +/- 0.04, respectively. For the 'late delayed' radiation response concerning paralysis and paresis the TER after 30 min at 41.1 degrees C and 42.1 degrees C were 1.25 +/- 0.10 and 1.31 +/- 0.07, respectively. The latent period for paralysis was not significantly affected. Pathological examination of the spinal cord after combined treatment of X-rays and hyperthermia showed focal demyelination with white matter necrosis and vascular injury in animals as an indication of 'early delayed' and 'late delayed' paralysis, respectively. This was not different from histopathological changes observed after irradiation alone.

Clearance of a Persistent Human Enterovirus Infection of the Mouse Central Nervous System by the Antiviral Agent Disoxaril

Enteroviruses can cause persistent central nervous system (CNS) infections in agammaglobulinemic individuals. Because these infections are rarely cured by passive administration of antibody, a chemotherapeutic approach would be advantageous. In this study, the efficacy of the antienterovirus (and antipicornavirus) drug disoxaril was demonstrated in a murine model of persistent enterovirus infection. Disoxaril is a hydrophobic antiviral compound that blocks picornavirus uncoating. The W-2 strain of human poliovirus type 2 (PV2) persists in the CNS of immunosuppressed mice and causes late paralysis. Mice were inoculated intracerebrally with PV2, immunosuppressed with cyclophosphamide, and treated intragastrically with disoxaril at 50, 100, or 200 mg/kg per day in two divided doses beginning on postinfection day 20. At 200 mg/kg per day, disoxaril significantly decreased the incidence of clinical disease, i.e., paralysis and death. Assays for virus revealed more rapid clearance of virus from the CNS in the drug-treated group. No drug-associated toxicity was observed. Residual isolates of virus were not drug-resistant, suggesting that the appearance of drug resistance during prolonged treatment may not be a clinical problem.

Aminoglycoside-induced biphasic hindlimb paralysis in the rat: A histological and electrophysiological assessment

The intrathecal injection of gentamicin into a human patient with gram-negative bacterial meningitis as well as its intracisternal injection into rabbits caused spongy-like lesions in the gray matter and tetraplegia in rabbits. To characterize this neurotoxic effect, gentamicin was injected into the subarachnoid space of the lumbar spinal cord of the rat. A biphasic hindlimb paralysis ensued which consisted at first of a transient flaccid paralysis lasting 1 to 5 hr followed by a permanent flaccid paralysis which developed after 24 to 36 hr. The initial paralysis occurred simultaneously with the transient loss of reflex transmission through the cord but in the absence of lesions in the spinal cord or physiological alterations of neuromuscular transmission and muscle contraction. The onset of the second phase of paralysis occurred concomitant with changes in reflex transmission and appearance of lesions. Loss of neuromuscular transmission and appearance of signs of denervation (e.g., depolarization, alteration in action potential parameters, and chemosensitivity) appeared after the second phase of paralysis was established. Both the initial transient and late permanent paralysis originated in the spinal cord. The early transient paralysis appears to be due to a central block of transmission while the late paralysis apparently resulted from neuronal damage. The neurotoxic effects of aminoglycosides on neuronal elements in the spinal cord resulted in secondary effects (signs of denervation) in hindlimb muscles.

Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: II. Virologic studies.

An attenuated human poliovirus infection of cyclophosphamide (CY)-treated mice resulted in a persistent CNS infection. Persistence in asymptomatic animals occurred in 46% of CY-treated mice but in only 3% of untreated animals, and was confined primarily to the brain. Virus replication in the brain peaked by day 3 for all inoculum dilutions, but was lower with diluted virus. High virus titers in the spinal cord were found only in paralyzed animals and occurred late in the infection following inoculation of diluted virus. Thus, the level of virus replication in the brain was directly related to the amount of virus inoculated, and was correlated with the rapidity of virus transit to the spinal cord and the incubation time to paralysis.

Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: I. Clinical, pathologic, and immunologic studies.

An attenuated human poliovirus infection of cyclophosphamide (CY)-treated mice was developed as a model of persistent CNS enterovirus infections and as an investigation of the interaction of virus with motor neurons during persistence. Ten percent of mice inoculated intracerebrally with undiluted virus developed clinical disease by day 90, but of those treated with CY, 80% developed disease. At higher virus dilutions plus CY there was a marked increase in the incubation period. The latest onset of clinical disease occurred on day 146. Only paralyzed animals had pathologic changes in the spinal cord and virus antigen in anterior horn cells. Neutralizing antibodies were suppressed by CY, as were humoral and cellular immune responses to other antigens.

The Polyvalency of Crotalidic Antivenins

Summary With American pit viper venoms the fatal dose for 20 gram mice injected intraperitoneally approximates that for 350 gram pigeons injected intravenously. No difference in time of onset and character of paralysis from very toxic and less toxic venoms, such as was observed in pigeons, was seen in mice. Venoms causing late paralysis and showing better neutralization by “Cascabel” antivenin in the pigeon are also better neutralized by this antivenin in the mouse. Certain bothropic venoms are equally well neutralized by the two types of antivenin. Certain foreign true viper venoms are neutralized to some extent by both types of antivenin, others little if at all.

Preparation and refining of diphtheria toxin-antitoxin

The mixture has been readjusted so that after standing eight months and longer, late paralysis will occur when the mixture is injected into guinea pigs. This is done by adding to each L+ dose one unit of a properly aged antitoxin. When five mils of this mixture is injected into guinea pigs acute death occurs within four or five days. The mixture is then stored in a refrigerator for a month to six weeks for stabilizing.On reinjecting five mils, after storage, the guinea pigs die of late paralysis after twenty to twenty-five days. It is then properly balanced and safe for distribution. Prepared as stated it retains its balance eight months and possibly much longer and its practically full immunizing value at least a year. What slight deterioration occurs takes place equally in the toxin and antitoxin and therefore there is no danger of the mixture becoming toxic.Constitutional disturbances are frequent. They are usually observed in adults, especially in those who give a pseudo Schick reaction. These disturb...

TARDY OR LATE PARALYSIS OF THE ULNAR NERVE

The type of neuritis which is the subject of this paper is peculiar, in that it develops many years after fractures and dislocations about the elbow joint. For this reason it has been termed tardy or paralysis. Usually, the injury to the joint has been received in childhood, the first symptoms of ulnar neuritis making their appearance in adult life. Thus, an interval which may vary from six to thirty-five years elapses between the initial injury and the first symptoms of ulnar neuritis, which are then gradually progressive. This remarkably long latent period excludes the group of cases, not uncommon, in which secondary paralysis follows redundant callus formation, vicious union, or other mechanical complications of fracture which jeopardize the integrity of neighboring nerve structures. The curious, and at the same time characteristic, feature of the late paralysis is its appearance so long after reception of the original injury that