Clinical Research

Failure of Single-Unit Neuronal Activity to Differentiate Globus Pallidus internus and externus in Parkinson Disease
J. Neurosurg. 97 119-128 (2002).
Steven J. Schiff, M.D., Ph.D., Brian K. Dunagan, and Robert M. Worth, M.D., Ph.D.
Object. The authors examine the validity of single-unit neuronal recordings as a method of differentiating the globus pallidus internus (GPi) from GP externus (GPe) in Parkinson Disease.
Methods. One hundred twenty-eight recordings of apparent single-unit activity used to help guide final electrod placement in eight patients who underwent pallidotomy were analyzed using sophisticated spike sorting methods, and 185 enurons were characterized for mean firing frequency and percent of firing within bursts. In adiition, the total spectral power was calculated on the full measured waveform for each of 128 samples without spike sorting. No correlation was identified between these measures of neuronal activity and depth within the GP.
Conclusions. These results call into question the validity of relying on single-unit activity and mciroelectrode recordings in the operating room to localize lesion or electrode placement withing the GPi during stereotactic pallidal surgery.

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Brain Chirps: Spectrographic Signatures of Epileptic Seizures
Clinical Neurophysiology 111 953-958 (2000).
Steven J. Schiff, David Colella, Gary M. Jacyna, Elizabeth Jughes, Joseph W. Creekmore, Angela Marshall, Maribeth Bozek-Kuzmicki, George Benke, William D. Gaillard, Joan Conry, and Steven R. Weinstein
Objective: A chipr is a brief signal within which the frequency content changes rapidly. Spectrographic chirps are found in signals produced from many biological and physical phenomena. In radar and sonar engineering, signals with chirps are used to localize direction and range to the signal source. Although characteristic frequency changes during epieptic seizures have long been observed, the correlation with chirps and chirp technology seems never to have been made.
Methods: We analyzed 19 404 s (1870 s of which were from 43 seizures) of intracranially (subdural and depth electrode) recorded digital EEG from 6 patients for the presence of spectral chirps. Matched filters were constructed from methods in routine use in non-medical signal processing applications.
Results: We found that chirps are very sensitive detectors of seizures (83%), and highly specific as markers (no false positive detections). The feasibility of using spectral chirps as matched filters was demonstrated.
Conclusions: Chirps are highly specific and sensitive spectrographic signatures of epileptic seizure activity. In addition, chirps may serve as templates for matched filter design to detect seizures, and as such, can demonstrate locatization and propagation of seizures from an epileptic focus.

Predicting PTH Pluses and Patterns in Osteoporosis
J. Clin. Invest. 95 2433(1995).
Leonard J. Deftos and Steven J. Schiff

FDG-PET in Children and Adolescents with Partial Seizures: Role in Epilepsy Surgery Evaluation
Epilepsy Research 20 77 (1995).
W.D. Gaillard, S. White, B. Malow, R. Flamini, S. Weinstein, S. Sato, C. Kufta, S. J. Schiff, O. Devinsky, S. Fazilat, P. Reeves, W.H. Theodore
We used FDG-PET to measure interictal glucose metabolism in 16 children and adolescents (mean age 14.7 years) with complex partial seizures (CPS) (mean seizure onset age 5.0 years). Video-EEG localized the epileptic foci. Glucose metabolism was determinism in 14 paired anatomic areas using a standard template. PET hypometabolism was defined as greater 15% asymmetry. Nine of the 13 (69%) patients with unilateral EEG focus had regional hypometabolism ipsilateral to the epileptogenic zone. Three subjects had bilateral EEG foci; all had nonfocal PET. MRI (15 patients) concurred with EEG and PET in two, and was normal in seven of nine with focal hypometabolism. One of seven patients with normal PET had a focal MRI abnormality. FDG-PET results are similar to those found in adults, but are present earlier in the natural history of CPS (9.7 vs 22.2 years duration epilepsy) than previously reported. The presence of FDG-PET hypometabolism may be associated with a poor response to drug treatment. PET can identify metabolic abnormalities associated with epileptic foci in children and adolescents and is useful in directing surgical intervention for the control of refractory complex partial epilepsy.

Quinolinic Acid in Tumors, Hemorrhage and Bacterial Infections of the Central Nervous System in Children
J. Neurological Science 133 112 (1995).
Melvyn P. Heyes, Kuniaki Saito, Sheldon Milstein, and Steven J. Schiff
A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation. The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage. Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents. CSP QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors. CSP l-kynurenine levles increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxyenase. The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections. The cytokines tumor necrosis factor-alpha and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS. Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted.

An Experimental Study of Reflex Variability in Selective Dorsal Rhizotomy
J. Neurosurg. 81 885 (1994).
Arnold D.C. Rivera, Tim Burke, Steven J. Schiff, and Ira P. Weiss
Significant problems regarding the measurement technique currently used to choose nerve roots for sectioning in the selective dorsal rhizotomy procedure have recently been reported. To better understand the source of these problems, a series of six experiments was performed in which the selective rhizotomy technique was applies to cats that were either intact, decerebrate, or spinalized. Measurements were made before and after partial rhizotomy. In decerebrate preparations, large, spontaneous changes in reflex threshold were observed over short periods of time, especially after partial rhizotomy was performed, and threshold changes greater than 1000% could be observed over 10-minute periods. Using constant-current stimulation of the dorsal root at threshold, the response of each ipsilateral leg muscle demonstrated frequent changes, and changes coincided with the variability in threshold estimation. In addition, very low thresholds were measured (0.1 to 0.25 mA) in half (3 to 6) of these experiments, these measurements being well below the currents customarily used for intraoperative decision making. Stimulation at twice threshold was found to consistently increase the pathological quality of the responses observed. Although intact animals never displayed contralateral responses when stimulated at threshold, such contralateral responses could readily be elicited at twice threshold. These laboratory results raise further doubts regarding the reliability of the measurement techniques now widely used for selective dorsal rhizotomy..

Response to Neurosurgical Forum: Dorsal Rhizotomy: To Monitor or Not to Monitor?
J. Neurosurg. 80 771 (1994).
Steven J. Schiff and Ira P. Weiss
Response to a letter to the editor.

Case Report: Use of Recombinant Human Erythropoietin to Aviod Blood Transfusion in a Jehovah's Witness Requiring Hemispherectomy
J. Neurosurg. 79 600 (1993).
Steven J. Schiff and Steven L. Weinstein
The use of perioperative human recombinant erythropoietin is described in a Jehovah's Witness patient. Despite significant anemia, the child's hematocrit was sufficiently increased by the use of erythropoietin so that a two-stage hemispherectomy could be performed without blood transfusion.

Reflex Variability in Selective Dorsal Rhizotomy
J. Neurosurg. 79 346 (1993).
Ira P. Weiss and Steven J. Schiff
The variability of reflex responses during selective dorsal rhizotomy was studied in eight children between the ages of 3 and 7 years. For a given dorsal root or rootlet, the electrical reflex threshold and response varied considerably when observed over several minutes. Changes in electrode pressure, mechanical dissection of the root, and reflex spatial facilitation were all found to contribute to the variability. Even when electrode pressure was held constant, intrinsic spinal cord reflex variability substantially weakened the predictability of the intraoperative selection method used during this surgery.

A Surgeon's Risk of AIDS
J. Neurosurg. 73 651 (1990).
Steven J. Schiff
A probabilistic model is used to estimate the cumulative risk to surgeons from human immunodeficiency virus (HIV). Recent data suggest that the probability of infection following percutaneous inoculation is about 1 in 250 cases. Several studies suggest that the frequency of percutaneous injury in surgery is at least 1 in 40 cases, for some as high as 1 in 20 cases. Assuming that on the average a surgeon will perform 350 operations per year and will practice for 30 years, the cumulative risk of HIV infection will depend on the prevalence of HIV infectio in the surgical population. For HIV prevalences of 1 in 100 to 1 in 10, the cumulative risk per surgeon ranges from 1 in 100 to 1 in 5, respectively. Based on these risk estimates, it is crucial to decrease the frequency of percutaneous injury. The case is made for substantial improvements in barrier protection and modification of surgical technique.

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