Spectrum of patients with EMG features of polyradiculopathy without neuropathy

We reviewed the medical records of 233 patients having electrodiagnostic evidence of polyradiculopathy. Patients with polyneuropathy or incomplete diagnostic evaluation were excluded. A clinical diagnosis was secured in 92 of the 118 remaining patients. Patients were separated into three groups based upon the anatomic location of root involvement: extradural (55), intradural-extraaxial (23), and intraaxial (14). Collectively, patients with intradural-extraaxial disorders had earlier disease onset, shorter symptom duration, and a higher disability score compared with the intraaxial or extradural groups. Pain was an initial complaint in 50 of 55 patients with extradural lesions, 20 of 23 with intradural-extraaxial disease, but only in 4 of 14 with intraaxial involvement. CSF abnormalities and reduced compound muscle action potential amplitudes were more common in the intradural-extraaxial group. We conclude that the anatomic localization of root involvement in patients with polyradiculopathy can be suggested by a combination of clinical, laboratory, and electrodiagnostic features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50147/1/880130112_ftp.pd

Zonisamide (CI-912) and Cognition: Results from Preliminary Study

Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (l,2-benzisoxazole-3-methane-sulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations >30 jjug/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p < 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects. RESUMEN En un estudio piloto realizado para valorar la eficacia de la zonisamida (1,2-Bencisoxazol-melanosulfonamida [CI-912]), un nuevo compuesto anticonvulsive se han evaluado unos 9 pa-cientes con ataques parciales refractarios al tratamiento. Se de-terminÓ la capacidad cognitiva anterior al tratamiento y se re-pitio 12 y 24 semanas despuÉs del tratamiento con zonisamida. Con concentraciones plasmÁticas mÍnimas estables per encima de 30 mcg/ml, la zonisamida afectÓ las funciones cognitives especÍficas tales como la adquisiciÓn y consolidaciÓn de nueva informaciÓn. El material aprendido previamente, tal como el vo-cabulario, y las funciones psicomotoras no se afectaron. El aprendizaje verbal se modificÓ mientras que el aprendizaje visuo-perfectivo no se modificÓ. Estos efectos cognitivos se ob-servaron en ausencia de los habituales signos y sÍntomas clÍnicos de toxicidad. Se encontrÓ una relaciÓn lineal entre la alteraciÓn de las posibilidades cognitivas y la concentraciÓn plasmÁtica mÍnima (r = -0.73, p < 0.05). Estos hallazgos tambiÉn sugieren el desarrollo de una tolerancia a los efectos cognitivos adversos. ZUSAMMENFASSUNG 9 Patienten mit rezidivierenden Partial-AnfÄllen wurden in einer Pilotstudie mit einer neuen antiepileptischen Substanz: Zonisamide untersucht. Die kognitiven Funktionen wurden vor der Behandlung mit Zonisamide geprtÜft und nach 12 und 24 Therapiewochen mit Zonisamide wiederholt. Bei einem Min-destplasmaspiegel von 30 mcg/ml schien Zonisamide spezifische kognitive FÄhigkeiten wie Aufnahme und Speicherung neuer In-formationen zu beeintrÄchtigen. Vorher gelernte Inhalte wie sprachliche und psychomotorische Fertigkeiten wurden nicht beeinflußt. Verbales Lernen war ebenfalls betroffen, wÄhrend visuell, perzeptives Lernen nicht verschlechtert war. Diese BeeintrÄchtigung kognitiver Funktionen wurde bei fehlenden klinischen Intoxikationszeichen beobachtet. Eine lineare Bezie-hung zwischen Verschlechterung kognitiver FÄhigkeiten und Mindest-Plasmaspiegel konnte hergestellt werden (r = -0,73; p < 0,05). Allerdings lassen die Ergebnisse auch auf eine GewÖhnung an diese unerwÜnschten Nebenwirkungen schließen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65995/1/j.1528-1157.1987.tb03624.x.pd

Pilot Study of Zonisamide (1,2-Benzisoxazole-3-methanesulfonamide) in Patients with Refractory Partial Seizures

A new anticonvulsant compound, zonisamide (1,2 benzioxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were high than plasma concentrations because of red blood cell binding. steady-state plasma concentrations were high than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal system were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day. RÉSUMÉ Un nouveau produit anticonvulsivant, le zonisamide (1,2 benziosoxazole-methylsulfonamide) a ÉtÉ administrÉÀ 10 adultes atteints de crises partielles non contrÔlÉes par le traitement mÉdical. AprÈs une dose unique orale de 400 mg, le pic du taux plasmatique survient en moyenne 2 h 1/2 aprÉs l'ingestion, et la clairance plasmatique moyenne est de 2,34 litres par heure. les concentrations sanguines totales sont plus ÉlevÉes que les concentrations plasmatiques, en raison de la liaison aux globules rouges, les concentrations plasmatiques À l'État d'equilibre sont plus ÉlevÉes que celles que l'on peut dÉdurie d'un modÈle de cinÉtique linÉaire. Chez la plupart des patients, la frÉquence des crises a ÉtÉrÉduite par la substitution du zonisamide au traitement antiÉpileptique standard. Des effets secondaires doses-dÉpendants et rÉversibles ont ÉtÉ observÉs au niveau du systÈme nerveux central et du tube digestif. La plupart des patients ont tolÉrÉ des doses entre 5,2 et 12,5 mg/kg de poids par jour. RESUMEN En 10 adultos con ataques parciales refractarios a1 tratamiento mÉdico, se ha estudiado la acciÓn de un nuevo compuesto anticonvulsivo, la zonisamida (1,2 benzisoxazol-metanosulfonamida). Tras la ingestiÓn de una sola dosis oral de 400 mg., se alcanzaron los niveles pico en plasma en un promedio de 2.8 horas desputs de la dosis y el aclaramiento medio del plasma fuÉ de 2, 34 litros/hora. Las concentraciones en sangre fueron mÁs altas que las plasmÁticas debido a que la medicaciÓn se ligaba a los hematies. Las concentraciones plasmÁticas estables fueron mÁs altas que las previsibles de un modelo cinÉtico lineal. En la mayorÍa de los pacientes la frecuencia de los ataques se redujo despuÉs de cambiar la medicaciÓn antiepilÉptica standard por la zonisamida. TambiÉn se observaron los efectos colaterales sobre el tracto gastrointestinal y el sistema nervioso central que estaban relacionadas con la dosis y eran reversibles. La mayor parte de los pacientes tolerÓ dosis que oscilaban entre 5.2 y 12.5 mg/kg/dÍa. ZUSAMMENFASSUNG Ein neues Antikonvulsivum, Zonisamid (1,2 Benzisoxazol-Methansulfonamid) wurde bei 10 Envachsenen mit therapieresistenten PartialanfÄllen gesucht. Nach einer oralen Einzeldosis von 400 mg wurden Plasmaspitzenwerte im Durchschnitt nach 2, 8 Stunden erreicht. Die mittlere Clearance aus dem Plasma betrug 2, 34 L/Stunde. Ganzblutkonzentrationen waren hÖher als Plasmakonzentrationen aufgrund der Bindung an die roten BlutkÖrperchen. Die steady-state Plasmakonzentrationen waren hÖher als bei einem linearen kinetischen Modell zu envarten. Bei den meisten Patienten konnte die Anfallsfrequenz nach Substitution eines Standardantiepileptikums durch Zonisamid reduziert werden. Es bestanden dosisabhÄngige, reversible, zentral-nervÖse und gastrointestinale Nebenwirkungen. Die meisten Patienten tolerierten Dosen zwischen 5, 2 und 12, 5 mg/kg/Tag.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65938/1/j.1528-1157.1985.tb05407.x.pd

Challenges of clinical trial design when there is lack of clinical equipoise: use of a response-conditional crossover design

Clinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators. When clinical equipoise is in question, innovative trial designs are needed to reduce ethical tension while satisfying regulators’ requirements. We report a novel response-conditional crossover study design used in a Phase 3, randomized, double-blind, placebo-controlled clinical trial of intravenous 10% caprylate-chromatography purified immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. During the initial 24-week period, patients crossed over to the alternative treatment at the first sign of deterioration or if they failed to improve or were unable to maintain improvement at any time after 6 weeks. This trial design addressed concerns about lack of equipoise raised by physicians interested in trial participation and proved acceptable to regulatory authorities. The trial design may be applicable to other studies where clinical equipoise is in question

Electrodiagnostic evolution of carcinomatous sensory neuronopathy

Sensory neuronopathy is a well-recognized remote effect of carcinoma. We report the clinical and electrodiagnostic evolution of a sensory neuronopathy in a patient with carcinoma of the lung. Serial electrophysiologic studies suggest transformation from normal peripheral nerve function through early posterior root involvement to absent sensory nerve function. Diffuse motor conduction abnormalities occurred late in the disease, perhaps reflecting motor axon changes associated with disuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50144/1/880120612_ftp.pd

Acute arsenic intoxication presenting as guillainbarrÉa-like syndrome

Arsenic-induced polyneuropathy is traditionally classified as an axonal-loss type, electrodiagnostically resulting in low amplitude or absent sensory and motor responses, relatively preserved proximal and distal motor conduction rates, and distal denervation. We report four patients with a subacute onset progressive polyradiculoneuropathy following high-dose arsenic poisoning. In three patients, early electrodiagnostic testing demonstrated findings suggestive of an acquired segmental demyelinating polyradiculoneuropathy. Serial testing confirmed evolution into features of a distal dying-back neuropathy. We hypothesize that arsenic toxicity and the resultant biochemical derangement of the peripheral nerve cell leads to subtle changes in axonal function that produce, initially, segmental demyelination and eventually distal axonal degeneration. Acute arsenic toxicity must be suspected in patients with clinical and electrodiagnostic features supporting Guillain-BarrÉ syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50138/1/880100203_ftp.pd