NOTES AND LETTERS
Neurological Research Lewis Robinson, MD As another full-time clinician, I must agree with Dr Stolzberg (Ann Neurol 3:563, 1978, replying to Plum F: The precarious position of neurological clinical investigation, Ann Neurol 2:359-363, 1977) that relatively little progress has been made in clinical neurology in the past decade. What progress there has been in day-to-day patient care does not seem to be the result of research carried o n in academic departments of neurology. Computerized axial tomography was not developed by a neurologist. The antiplatelet drugs were not developed by neurologists. T h e newer anticonvulsanr medications were not developed by neurologists. Neurologists have had essentially no role in developing intracranial bypass procedures for stroke, dorsal column stimulation, or cerebellar pacemakersmodalities which may be useful to our patients in the future. I think the research money that has gone to departments of academic neurology has been largely wasted. 1 think future funding should confine itself to the evaluation of new drugs and treatment and to a better delineation of the natural history of the various common neurological diseases. ~
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Author’s address: 1537 Avenue D, Billings, MT 59102.
Computed Tomography in Wilson Disease Report of 2 Cases -
Allan H. Ropper, MD, H. Paul Hatten, Jr, MD, and Kenneth R. Davis, M D Wilson disease is a protean illness in which the basal ganglia are predominantly affected. The red nucleus 131, dentate nucleus [2], brainstem structures [ 2 ] ,and frontal cortex [ 13 are occasionally damaged, as well as the lenticular nuclei and caudate head. Two patients with Wilson disease are reported who had computed tomographic scans demonstrating damage to all these structures in 1 case and minimal changes in the basal ganglia in the other.
Patient 1 A 19-year-old woman was seen for nervousness, labile affect, and difficulty writing. There was a history of jaundice
From the Departments of Neurology and Radiology, Massachusetts General Hospital, Boston, MA. Accepted for publication July 5, 1978. Address reprint requests to Dr Ropper, Department of Neurofogy, Massachusetts General Hospital, Fruit St, Boston, MA 02 114.
102
and anemia at age 15. An uncontrollable bleating inspiratory laugh developed. O n examination she sat stooped, stared, and had slow, hypophonic speech. Kayser-Fleischer rings were evident. There was diffuse cogwheeling rigidity, rapid alternating movements were slow and of small excursion, and she walked in a shuffling and halting manner. Ceruloplasmin was unmeasurable; urine copper was 560 pg per 24 hours. Despite cupruresis on penicillamine, she deteriorated over the ensuing 10 months, with a severe pseudobulbar state, aphonia, and bradykinesia with elements of both cogwheeling and spastic rigidity. Brainstem auditory evoked responses were delayed at the level of the pons. A CT scan (Fig IA) 21 months after the appearance of neurological symptoms demonstrated bilateral cavitation of the putamen, which had the form of slitlike, homogeneous, low-absorption abnormalities. A more diffuse bilateral area of abnormal low absorption was present in the remainder of the putamen, globus pallidus, head of the caudate, and dentate nucleus (Fig IB). These changes were associated with compensatory dilatation of the frontal horns and founh ventricle, respectively. There was minimal diffuse cortical atrophy, particularly of the frontal lobes.
Patient 2 A 24-year-old man was seen 4 months after he became reclusive and unsociable. A hand tremor appeared which interfered with his writing and work as a mechanic. There was impairment in balance, causing him to topple backward. He was alert and agile and had a brown corneal Kayser-Fleischer ring. Speech was slightly dysarthric. Tone was increased in the left arm and leg without cogwheeling. He walked on a 20 cm heel base with staggering. There were grasp and sucking reflexes. A prominent feature was an irregular, small-excursion, cloniclike tremor of the left hand and leg, which subsided at rest. The ceruloplasmin was 3 pg/dl and urine copper, 445 p g per 24 hours. A CT scan (Fig 2 ) done 4 months after the onset of symptoms demonstrated selective dilatation of the frontal horns and fourth ventricle secondary to bilareral atrophic changes in the head of the caudate and lenticular nuclei and in the dentate nuclei, respectively. There was minimal cortical atrophy of the frontal regions but no low absorption.
Discussion T h e pathological changes in Wilson disease range from microscopic focal degeneration to cavitation, mainly in the middle third of the putamen, following which it appears i n the anterior putamen and the caudate [ 1I. Because of this topography, horizontal brain sections, as obtained by C T scan, optimally demonstrate the tissue loss. The globus pallidus may be macroscopically spared. Destruction of the dentate nucleus I l l , red nucleus 131, cerebellar cortex, brainstem nuclei, and cerebral cortex, especially the frontal lobes 111, has been reported infrequently and o n l y in advanced cases prior to the use of penicillamine. Patient 1 had advanced pathological changes on C T scan, and no improvement occurred with penicillamine therapy in the subsequent months. The scan in this patient demon-
Neurological Research Lewis Robinson, MD As another full-time clinician, I must agree with Dr Stolzberg (Ann Neurol 3:563, 1978, replying to Plum F: The precarious position of neurological clinical investigation, Ann Neurol 2:359-363, 1977) that relatively little progress has been made in clinical neurology in the past decade. What progress there has been in day-to-day patient care does not seem to be the result of research carried o n in academic departments of neurology. Computerized axial tomography was not developed by a neurologist. The antiplatelet drugs were not developed by neurologists. T h e newer anticonvulsanr medications were not developed by neurologists. Neurologists have had essentially no role in developing intracranial bypass procedures for stroke, dorsal column stimulation, or cerebellar pacemakersmodalities which may be useful to our patients in the future. I think the research money that has gone to departments of academic neurology has been largely wasted. 1 think future funding should confine itself to the evaluation of new drugs and treatment and to a better delineation of the natural history of the various common neurological diseases. ~
~
~~
~
Author’s address: 1537 Avenue D, Billings, MT 59102.
Computed Tomography in Wilson Disease Report of 2 Cases -
Allan H. Ropper, MD, H. Paul Hatten, Jr, MD, and Kenneth R. Davis, M D Wilson disease is a protean illness in which the basal ganglia are predominantly affected. The red nucleus 131, dentate nucleus [2], brainstem structures [ 2 ] ,and frontal cortex [ 13 are occasionally damaged, as well as the lenticular nuclei and caudate head. Two patients with Wilson disease are reported who had computed tomographic scans demonstrating damage to all these structures in 1 case and minimal changes in the basal ganglia in the other.
Patient 1 A 19-year-old woman was seen for nervousness, labile affect, and difficulty writing. There was a history of jaundice
From the Departments of Neurology and Radiology, Massachusetts General Hospital, Boston, MA. Accepted for publication July 5, 1978. Address reprint requests to Dr Ropper, Department of Neurofogy, Massachusetts General Hospital, Fruit St, Boston, MA 02 114.
102
and anemia at age 15. An uncontrollable bleating inspiratory laugh developed. O n examination she sat stooped, stared, and had slow, hypophonic speech. Kayser-Fleischer rings were evident. There was diffuse cogwheeling rigidity, rapid alternating movements were slow and of small excursion, and she walked in a shuffling and halting manner. Ceruloplasmin was unmeasurable; urine copper was 560 pg per 24 hours. Despite cupruresis on penicillamine, she deteriorated over the ensuing 10 months, with a severe pseudobulbar state, aphonia, and bradykinesia with elements of both cogwheeling and spastic rigidity. Brainstem auditory evoked responses were delayed at the level of the pons. A CT scan (Fig IA) 21 months after the appearance of neurological symptoms demonstrated bilateral cavitation of the putamen, which had the form of slitlike, homogeneous, low-absorption abnormalities. A more diffuse bilateral area of abnormal low absorption was present in the remainder of the putamen, globus pallidus, head of the caudate, and dentate nucleus (Fig IB). These changes were associated with compensatory dilatation of the frontal horns and founh ventricle, respectively. There was minimal diffuse cortical atrophy, particularly of the frontal lobes.
Patient 2 A 24-year-old man was seen 4 months after he became reclusive and unsociable. A hand tremor appeared which interfered with his writing and work as a mechanic. There was impairment in balance, causing him to topple backward. He was alert and agile and had a brown corneal Kayser-Fleischer ring. Speech was slightly dysarthric. Tone was increased in the left arm and leg without cogwheeling. He walked on a 20 cm heel base with staggering. There were grasp and sucking reflexes. A prominent feature was an irregular, small-excursion, cloniclike tremor of the left hand and leg, which subsided at rest. The ceruloplasmin was 3 pg/dl and urine copper, 445 p g per 24 hours. A CT scan (Fig 2 ) done 4 months after the onset of symptoms demonstrated selective dilatation of the frontal horns and fourth ventricle secondary to bilareral atrophic changes in the head of the caudate and lenticular nuclei and in the dentate nuclei, respectively. There was minimal cortical atrophy of the frontal regions but no low absorption.
Discussion T h e pathological changes in Wilson disease range from microscopic focal degeneration to cavitation, mainly in the middle third of the putamen, following which it appears i n the anterior putamen and the caudate [ 1I. Because of this topography, horizontal brain sections, as obtained by C T scan, optimally demonstrate the tissue loss. The globus pallidus may be macroscopically spared. Destruction of the dentate nucleus I l l , red nucleus 131, cerebellar cortex, brainstem nuclei, and cerebral cortex, especially the frontal lobes 111, has been reported infrequently and o n l y in advanced cases prior to the use of penicillamine. Patient 1 had advanced pathological changes on C T scan, and no improvement occurred with penicillamine therapy in the subsequent months. The scan in this patient demon-
