normal, 4 American ALS, and 16 Guamanian ALS brain and spinal cord specimens. O n e American ALS patient had had an acute paralytic episode, clinically diagnosed as acute poliomyelitis, fifteen years previously.
PLEDs and Ny stagmus Retractorius Richard P. Brenner, MD, and Thomas J. Carlow, M D
Discussion A number of factors might explain our inability to detect polio sequences in the ALS samples tested. First, poliovirus may be present early in the course of the illness, but specimens examined at necropsy might contain little o r no residual viral nucleotide sequences. Second, the polio R N A (type 1, Mahoney) used as template for c D N A synthesis may have diverged to the extent that the probe would not recognize wild type poliovirus sequences. Despite previous reports of considerable polynucleotide divergence among the three antigenic types of poliovirus [S], little difference was detected between types I and I1 using S1 nuclease assays of cDNA-RNA hybrids. Third, poliovirus R N A may be present in ALS samples below the level of sensitivity of our assay. Using data from our reconstruction experiments, approximately 20 molecules of free positive strand RNA per cell would have to be present to be detected in this assay. In HeLa cells acutely infected with poliovirus, 0.67 - 3 . 7 3 x lo5 single-strand viral molecules are present per cell [2]. N o published data describe the viral RNA content of cell systems persistently infected with poliovirus. Supported by a grant from the Amyotrophic Lateral Sclerosis Society of America. We thank Dr D. Kacian for poliovirus 35.5 RNA and Dr Richard Johnson for polio-infected mouse brains.
References 1. Brinen R, Kohne D: Repeated sequences in DNA. Science 161:529-540, 1968 2. Hewlett M, Rozenblatt S, Ambros V, et al: Separarion and quantitation of intracellular forms of poliovirus RNA by agarose gel electrophoresis. Biochemistry 16:2763-2767, 1977 3. Kacian D, Myers J: Synthesis of extensive, possibly complete, DNA copies of poliovirus RNA in high yields at high specific activities. Proc Natl Acad Sci USA 73:2191-2195, 1976 4. Poskanzer D, Cantor H, Kaplan G: The frequency of preceding poliomyelitis in amyotrophic lateral sclerosis, in Norris FH, Kurland LT (eds):Motor Neuron Diseases. New York, Grune & Stratton, 1969, pp 286-290 5. Viola MV, Gann K L A rapid efficient method for extraction of nucleic acids from brain. J Neurochem (in press) 6. Viola MV, Gann KL, Scott C, et al: Absence of measles proviral DNA sequences in systemic lupus erythematosus. Nature 275:667-669, 1978 7. Viola MV, White L Murine leukemia virus-specific nucleotide sequences in normal and malignant cells. Nature 246:485-487, 1973 8. Young N, Hoyer B, Martin M: Polynucleotide sequence homologies among polioviruses. Proc Natl Acad Sci USA 6 ~ 5 4 8 - 5 5 5 , 1968 9. Zilkha KJ: Discussion o n motor neuron disease. Proc R Soc Med 55:1029, 1962
W e read with interest the article by Young et a1 (Periodic lateraked epileptiform discharges [PLEDs] and nystagmus retractorius. Ann Neurol 2:61-62, 1977) and have recently had an opportunity to evaluate a similar case.
A 65-year-old man with a history of seizures required intravenous dilantin therapy to control focal seizures, which initially consisted of left arm jerking and head and eye deviation to the left. The next morning the arm movement and head and eye deviation ceased, but he had bilaterally synchronous posterior retraction of both globes. An electroencephalogram showed PLEDs over the right hemisphere, most prominent in the frontal area. The posterior global retractory eye movements were temporally associated with the epileptiform discharges. A CT scan was normal, as were the cerebrospinal fluid and laboratory values. He experienced occasional focal seizures over the next several months. Two months later a nonenhancing decreased density was observed in the right frontal region on CT scan. This patient, like Young’s, had nystagmus retractorius without evidence of a brainstem lesion. It appeared from his second CT scan that a vascular lesion was responsible for the ocular oscillations and PLEDs. During brief periods in which the e y e movements ceased, our patient had normal ductions and versions-normal oculocephalic and pupillary signs which would tend to separate this type of retraction nystagmus from one secondary to a destructive lesion at the diencephalic-mesencephalic junction.
From the Department of Neurology, University of New Mexico School of Medicine, and the Veterans Administration Hospital, Albuquerque, N M 87131.
Notes and Letters
403
PLEDs and Ny stagmus Retractorius Richard P. Brenner, MD, and Thomas J. Carlow, M D
Discussion A number of factors might explain our inability to detect polio sequences in the ALS samples tested. First, poliovirus may be present early in the course of the illness, but specimens examined at necropsy might contain little o r no residual viral nucleotide sequences. Second, the polio R N A (type 1, Mahoney) used as template for c D N A synthesis may have diverged to the extent that the probe would not recognize wild type poliovirus sequences. Despite previous reports of considerable polynucleotide divergence among the three antigenic types of poliovirus [S], little difference was detected between types I and I1 using S1 nuclease assays of cDNA-RNA hybrids. Third, poliovirus R N A may be present in ALS samples below the level of sensitivity of our assay. Using data from our reconstruction experiments, approximately 20 molecules of free positive strand RNA per cell would have to be present to be detected in this assay. In HeLa cells acutely infected with poliovirus, 0.67 - 3 . 7 3 x lo5 single-strand viral molecules are present per cell [2]. N o published data describe the viral RNA content of cell systems persistently infected with poliovirus. Supported by a grant from the Amyotrophic Lateral Sclerosis Society of America. We thank Dr D. Kacian for poliovirus 35.5 RNA and Dr Richard Johnson for polio-infected mouse brains.
References 1. Brinen R, Kohne D: Repeated sequences in DNA. Science 161:529-540, 1968 2. Hewlett M, Rozenblatt S, Ambros V, et al: Separarion and quantitation of intracellular forms of poliovirus RNA by agarose gel electrophoresis. Biochemistry 16:2763-2767, 1977 3. Kacian D, Myers J: Synthesis of extensive, possibly complete, DNA copies of poliovirus RNA in high yields at high specific activities. Proc Natl Acad Sci USA 73:2191-2195, 1976 4. Poskanzer D, Cantor H, Kaplan G: The frequency of preceding poliomyelitis in amyotrophic lateral sclerosis, in Norris FH, Kurland LT (eds):Motor Neuron Diseases. New York, Grune & Stratton, 1969, pp 286-290 5. Viola MV, Gann K L A rapid efficient method for extraction of nucleic acids from brain. J Neurochem (in press) 6. Viola MV, Gann KL, Scott C, et al: Absence of measles proviral DNA sequences in systemic lupus erythematosus. Nature 275:667-669, 1978 7. Viola MV, White L Murine leukemia virus-specific nucleotide sequences in normal and malignant cells. Nature 246:485-487, 1973 8. Young N, Hoyer B, Martin M: Polynucleotide sequence homologies among polioviruses. Proc Natl Acad Sci USA 6 ~ 5 4 8 - 5 5 5 , 1968 9. Zilkha KJ: Discussion o n motor neuron disease. Proc R Soc Med 55:1029, 1962
W e read with interest the article by Young et a1 (Periodic lateraked epileptiform discharges [PLEDs] and nystagmus retractorius. Ann Neurol 2:61-62, 1977) and have recently had an opportunity to evaluate a similar case.
A 65-year-old man with a history of seizures required intravenous dilantin therapy to control focal seizures, which initially consisted of left arm jerking and head and eye deviation to the left. The next morning the arm movement and head and eye deviation ceased, but he had bilaterally synchronous posterior retraction of both globes. An electroencephalogram showed PLEDs over the right hemisphere, most prominent in the frontal area. The posterior global retractory eye movements were temporally associated with the epileptiform discharges. A CT scan was normal, as were the cerebrospinal fluid and laboratory values. He experienced occasional focal seizures over the next several months. Two months later a nonenhancing decreased density was observed in the right frontal region on CT scan. This patient, like Young’s, had nystagmus retractorius without evidence of a brainstem lesion. It appeared from his second CT scan that a vascular lesion was responsible for the ocular oscillations and PLEDs. During brief periods in which the e y e movements ceased, our patient had normal ductions and versions-normal oculocephalic and pupillary signs which would tend to separate this type of retraction nystagmus from one secondary to a destructive lesion at the diencephalic-mesencephalic junction.
From the Department of Neurology, University of New Mexico School of Medicine, and the Veterans Administration Hospital, Albuquerque, N M 87131.
Notes and Letters
403
