Biomedical subjects
Publications and source records attributed to D Moffie.
Three cases of aberrant nerve fibres in the spinal cord and medulla oblongata are described. The literature on these fibres is discussed and their possible role in regeneration. Different views on the possibility of regeneration or functional recovery of the central nervous system are mentioned in the light of recent publications, which are more optimistic than before.
A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.
A patient is described with a severe encephalopathy and hyperammonemia in absence of liver dysfunction, attributed to urine absorption into the systemic circulation due to suture line breakdown after bladder dome resection. At autopsy characteristic Alzheimer type II astrocytes were found in the basal ganglia.
Nine out of 14 patients treated with intraventricular methotrexate (MTX) for meningeal carcinomatosis from breast carcinoma and surviving more than 4 months developed disseminated necrotising leukoencephalopathy (DNL). All four patients who had received both intraventricular MTX and whole brain radiotherapy developed DNL. Five of the six patients who experienced an acute febrile reaction with mild encephalopathic signs following intraventricular administration of MTX developed DNL after a mean time of 5 months and a low mean dose of 44 mg MTX. DNL was also noted in two patients without a previous febrile reaction or whole brain radiotherapy, following prolonged intraventricular MTX therapy after a mean time of 19.5 months and a mean dose of 147 mg MTX. These findings confirm the hazards of (1) high cumulative doses of intrathecal MTX and (2) combined intrathecal chemotherapy and whole brain radiotherapy. This study also suggests a possible relationship between an early and transient febrile reaction during intraventricular administration of MTX and the development of DNL.
Description of 11 patients with congenital malformations of the spinal cord. Six of them were males, five females and the age varied from 7 to 70 years. Most of these cases produced clinical neurological signs indicating spinal cord disease in later life during an intercurrent disease. It was thought that changes in the bloodvessels and/or perfusion of the area of the spinal cord malformation was the ultimate cause of the neurological symptoms. An exact explanation of the origin of these developmental disturbances of the spinal cord remains unknown. Different hypotheses proposed in the literature, concerning these malformations, are not satisfactory.
We report a patient with a Wallenberg's lateral medullary syndrome in which pain was a prominent feature. This led to substitution of the original and correct diagnosis by that of a thalamic syndrome for which a prefrontal leucotomy was performed. The patient died some years later from a myocardial infarction and autopsy was performed. In the dorsolateral part of the medulla oblongata a cavity was found in which aberrant nerve fibres with neuroma-like formations could be seen. These fibres coursed along blood vessels, and penetrated from the surface of the medulla oblongata. On the base of the clinico-pathological correlations, it is conjectured that destruction of the lateral reticular formation cannot be the sole cause of the severe pain.
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The available clinical and pathological data of 5 cases with solitary midbrain metastasis including 2 of the present study are reviewed. Progressive dementia occurred in one case and mild dementia in another who also developed ocular symptoms. Ocular symptoms with sensory and coordination disturbances were seen in one, and only ocular symptoms in another case. Right-sided hemiplegia of 5 years duration occurred in the remaining case. Survival in tegmentum lesions is short.
Three cases of intramedullary metastases and one of a metastasis into the medulla oblongata are described. In two cases the primary tumour was a bronchial carcinoma and in one case a carcinoma of the breast. In one patient a primary tumour could not be found. The literature on this condition is reviewed and the difficulties of clinical diagnosis are discussed. The question remains unanswered as to the mechanism by which these tumour-cells reach the spinal cord and there is, as yet, no satisfactory explanation for the relative rare occurrence of these metastases.
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In 9 patients with Wallenberg's lateral medullary syndrome, one patient with a midbrain lesion involving the right side of the tegmentum, and 2 patients with a thalamic lesion, corneal reflexes were investigated by a new electromyographic technique. The electrophysical results were compared with the results obtained by clinical observation. In the lateral medullary lesions the electrophysiologically obtained reflex responses showed four types of abnormality. Type A consisted of a bilateral delay and type B a bilateral absence of the corneal reflex response to stimulation on the affected side in combination with a normal reflex response on both sides when the cornea on the normal side was stimulated. Type C, which was present in one case, and type D which was seen in 3 cases, consisted of a bilateral absence of the corneal reflex upon stimulation on the affected side; stimulation on the unaffected side produced a normal reflex response on the intact side in combination with, respectively, a delay or absence of the corneal reflex response on the affected side. Comparison of the clinical observations with the electrophysiological findings revealed minor discrepancies in type A and B abnormalities. However, the electrophysiological type C and D abnormalities were not detected by clinical observation. These findings demonstrate that electrophysiological recording of the corneal reflex may reveal clinically undetectable abnormalities. From the electrophysiological findings it is concluded that the corneal reflex is conducted along medullary pathways running both ipsilaterally and contralaterally from the stimulated side before connecting, respectively, with the ipsilateral and contralateral facial nucleus. From the anatomical findings it is suggested that the ascending pathways from the spinal fifth nerve complex to the facial nuclei are located in the lateral reticular formation of the lower brain-stem. The normal corneal reflex responses in the presence of thalamic and midbrain lesions involving nociceptive fibres in the trigeminothalamic tract do not support a previously postulated long-loop reflex arc passing through this tract. The suprabulbar influence upon the corneal reflex is discussed.
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Description of four cases of cordotomy for intractable pain in which autopsy could be performed. In two of the cases the lesion had been placed (unintentionally) in the posterior quadrant of the spinal cord with good results as to the abolishing of pain. It is concluded that the conduction of pain and temperature stimuli is not restricted to the anterolateral part of the spinal cord but that this conduction may also take place along fibres in the posterolateral quadrant. A further conclusion is that the results of cordotomy are related to the number of cut fibres.
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Re-examination of eight patients in whom bulbar trigeminal tractotomy had been performed 13 to 15 years previously showed that four had no complaints, and the other four had only very slight complaints about pain. In two patients a Spiller-Frazier operation had been performed after tractotomy, in two patients exairesis of the infraorbital or supraorbital nerve had been done. As bulbar trigeminal tractotomy is a major operation and the risk of recurrence is substantial, the indications for this type of operation have to remain very restricted. Theories to explain the recovery of sensation are discussed. It is possible that regeneration of transected fibres is responsible for the loss of analgesia.
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