Early history of development of boron neutron capture therapy of tumors.

The stable isotope 10B has a peculiarly marked avidity to capture slow neutrons whereupon it disintegrates into a lithium and a helium atom. These give up the 2.4 MeV of disintegration energy which they share within 5 and 9 microns of the 10B atom respectively. This means that the cell closest to the 10B atom bears the brunt of its atomic explosion. The objective of the tumor therapist is to find a carrier molecule for the boron atom which will concentrate in the tumor. Although a number of investigators saw the peculiar advantage of this selective tactic to achieve destruction of a species of unwanted cells, no success in animal studies was achieved until 1950. Sweet and colleagues found that the capillary blood-brain barrier keeps many substances out of the normal brain but that the gliomas had much less of such a barrier. He, Brownell, Soloway and Hatanaka in Boston together with Farr. Godwin, Robertson, Stickley. Konikowski and others at the Brookhaven. National Laboratory worked partially in collaboration and partly independently. We irradiated at 3 nuclear reactors several series of glioma patients with no long-term remission, much less a cure being achieved. Hatanaka on his return to Japan kept BNCT alive by treating a total of 140 patients with various brain tumors. Beginning in 1972, Mishima and colleagues have achieved useful concentrations of 10B-borono-phenylalanine, an analogue of the melanin precursor tyrosine, for BNCT of melanomas.

Pain--old and new methods of study and treatment.

In the last 5 years several remarkable methods for localizing precisely a wide range not only of specific motor and sensory functions but as well of more complex mental phenomena in the domain of cognitive functions have been demonstrated to evoke sharply localizable responses. In pain, positron emission tomography (PET) scanning has been used to show that the anterior gyrus cinguli is an integral component of the pain system. The PET technique suffers from a limitation of both spatial and temporal resolution, which permits only accurate center of mass coordinates of activated regions. Functional mapping of the brain by nuclear magnetic resonance has been achieved with techniques depicting specific brain areas in action during a mental process. These techniques open up an entirely new domain for study and treatment of many problems linked to cognition including many in whom pain is a central feature. The many cerebral cortical areas involved in pain make it unlikely that any ablative procedure will achieve long sustained pain relief. The dual objective of relief of both pain and suffering is probably going to be attained only by activation of pain suppressor mechanisms. This may well require the added knowledge accessible only by functional magnetic resonance imaging.

History of surgery for craniopharyngiomas.

Craniopharyngiomas, although histologically benign, are usually so intimately associated with the hypothalamus that total extirpation of these tumors was generally followed by death from hypotension and gross endocrine deficiencies. During the first half of the present century, those recording their tribulations include the famous names of Grant, Bailey, Bucy, Peet, Kahn, Olivecrona, Norlen, Sjöqvist, Rougerie and Northfield. Matson and Sweet were the first to achieve major reductions in mortality by giving massive doses of cortisone plus meticulous dissection, which took advantage of the reactive glial envelope which surrounds the great majority of these tumors.

Monoamines in the brain cerebrospinal fluid of facial pain patients.

The purpose of the study was to assay monoamines in cerebrospinal fluid (CSF) obtained from the trigeminal cistern of 64 patients with intractable facial pain. The CSF was analyzed for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), end-product markers of activity for the dopamine, serotonin, and norepinephrine systems, respectively. HVA averaged 121 ng/mL in these facial pain patients, compared to 150 to 550 ng/mL in 10 studies of ventricular brain CSF in assorted psychiatric and pain patients. 5-HIAA averaged 29 to ng/mL in our facial pain patients compared to 60 to 120 ng/mL in nine studies of ventricular brain CSF in assorted psychiatric and neurological patients. Trigeminal cistern CSF MHPG averaged 9 ng/mL, similar to the range of 13 studies of lumbar CSF of assorted psychiatric and pain diagnoses. These results indicate that (1) the electrochemical detection method provides a unique way of accurately measuring nanogram concentrations of multiple monoamines in a little as 0.25 mL of CSF; (2) trigeminal cistern and posterior fossa brain CSF monoamine metabolites reflect a different profile of dopaminergic and serotonergic functioning in these facial pain patients from that previously reported with lumbar CSF measurements of other patients; and (3) trigeminal sensory ganglion or brain dopamine and serotonin systems may be concomitantly dysfunctional in intractable facial pain.

Trigeminal facial pain: a model of peptides and monoamines in intracerebral cerebrospinal fluid.

A biochemical model of chronic trigeminal facial pain with elevated substance P (SP) and co-dysfunctional dopamine (DA), norepinephrine (NE) and purinergic systems is proposed. The serotonergic system is hypoactive as judged by low 5 hydroxyindoleacetic acid (5HIM). In distinction, intracerebral opioids may not be dysfunctional in facial pain as measured by normal levels of beta endorphin (BE). The neuropeptides somatostatin (SOM), cholecystokinin (CCK), met and leu-enkephalin (MENK, LENK) have very small picogram concentrations in these pain patients, but no definite conclusion can be reached on their role in trigeminal pain, alone or with monoamines, because of the small numbers, both sample size and concentrations. Interpretive obstacles to such human neurochemical studies suggest that future work might move to human clinical trials comodulating SP down, inhibitory peptides (SOM, CCK) up, and enhancing monoamine systems.

Pre-trigeminal neuralgia.

Eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed "pre-trigeminal neuralgia." These patients described their prodromal pain as a toothache or sinusitis-like pain lasting up to several hours, sometimes triggered by jaw movements or by drinking hot or cold liquids. Typical trigeminal neuralgia developed a few days to 12 years later, and in all cases affected the same division of the trigeminal nerve. Six additional patients experiencing what appeared to be pre-trigeminal neuralgia became pain-free when taking carbamazepine or baclofen. Recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures.

Entrapment of the C2 root and ganglion by the atlanto-epistrophic ligament: clinical syndrome and surgical anatomy.

Two cases of progressive, occipital lancinating pain and dysesthesias associated with a sensory deficit of the C2 dermatome are presented. Symptoms were relieved, and C2 sensory function restored by releasing a hypertrophied atlanto-epistrophic ligament entrapping the C2 root and ganglion. The normal anatomy and abnormal surgical findings are described. C2 entrapment by the atlanto-epistrophic ligament is discussed in reference to other C2 lesions causing occipital pain. We conclude that some patients whose progressive occipital pain is accompanied by a C2 sensory deficit are suffering from entrapment of the C2 root and ganglion amenable to surgical decompression.

Distribution of 10B after infusion of Na210B12H11SH into a patient with malignant astrocytoma: implications for boron neutron capture therapy.

If a sufficient concentration of the stable isotope 10B is introduced into a neoplasm, radiation therapy can be effected by short-range heavy charged particles from the disintegration of 10B by slow neutrons. Brain tumors were irradiated postoperatively by Hatanaka and co-workers in Japan using a 1 to 2 hour intraarterial infusion of 10B-enriched Na2B12H11SH (Na210B12H11SH) before exposure of the tumor-bearing area of the brain to slow neutrons from a 100 kilowatt nuclear reactor. The clinical outcome of such boron neutron capture therapy has been favorably impressive in some patients, but its efficacy in brain tumors needs improvement. In our study, a terminally ill patient with malignant astrocytoma was infused intravenously with Na210B12H11SH for 25 hours. The postmortem distribution of 10B in unfixed, frozen, tumor-bearing brain and spinal cord tissues was studied by comparing representative cryostat sections of these specimens with neutron-induced heavy charged particle radiographs of the same sections. Preferential accumulation of 10B was observed in the tumor, with relatively little accumulation of 10B in the parenchyma of the central nervous system.

Percutaneous methods for the treatment of trigeminal neuralgia and other faciocephalic pain; comparison with microvascular decompression.

The treatment of trigeminal neuralgia by the minor percutaneous invasive procedures of selective thermal rhizotomy, glycerol injection, and balloon compression in the middle cranial fossa are compared with the open operations of compression in the middle fossa and MVD in the posterior fossa. A conservative end point for any one of the three percutaneous methods is recommended as the first invasive procedure in this disorder. The management of the facial pains in multiple sclerosis, cancer, posttraumatic and postherpetic pain, migrainous neuralgia (cluster headache), and vagoglossopharyngeal neuralgia is also discussed.

Deafferentation pain in man.

Pains of various etiologies are described in so many overlapping ways that verbal descriptions alone do not permit a valid distinction between those pains associated with neurological injury (with or without sensory loss) and those associated with neurological compression. Nor does the fact of some sensory loss plus pain constitute a useful classification to determine either the mechanism of the pain or its treatment. Progress is more likely to ensue if we seek to characterize in detail each type of painful lesion. Evidence for these conclusions is drawn from cases of brachial plexus injury, trigeminal rhizotomy and tractotomy, postcordotomy dysesthesia and central pain treated by regional guanethidine block. Examples of the value of totally innovative approaches are drawn from the physics of elementary particles.

Dangerous rises in blood pressure upon heating of trigeminal rootlets; increased bleeding times in patients with trigeminal neuralgia.

During radiofrequency (RF) heating of trigeminal rootlets, we regularly measured blood pressure rises to 250 to 300 mm Hg, confirming two previous reports. We also found abnormally increased bleeding times in 12% of 127 patients awaiting operation for trigeminal neuralgia. These two facts probably explain 6 fatalities and 2 lasting hemiplegias from intracranial bleeding unrelated to vascular puncture by the needle electrode during RF procedures for trigeminal neuralgia. We recommend correction of the abnormal bleeding time and control of the blood pressure rises by i.v. sodium nitroprusside.

Problems with retrogasserian glycerol in the treatment of trigeminal neuralgia.

Following glycerol injections for trigeminal neuralgia. Håkanson, Lunsford, Apfelbaum, Beck and Lobosky and Dieckmann, among others, report that few patients have sensory loss and dysesthesia and a high percentage have sustained gratifying relief. Such was not our experience or that of Laitinen, Price, Siegfried, or Takusagawa, among others. Our own disappointing results re initial failures to achieve relief, significant sensory loss including corneal anesthesia and some dysesthesias in 77 patients are described.

Deafferentation pain after posterior rhizotomy, trauma to a limb, and herpes zoster.

After incisional or alcoholic destruction of trigeminal posterior rootlets, constant dysesthesias of major degree referred to some part of the markedly denervated zone develop in 5 to 15% of the patients. The full severity may not appear for weeks or months. There is no allodynia or hyperpathia of the denervated zone. Bulbar trigeminal tractotomy with sparing of touch sensation produces severe dysesthesias in a tiny percentage of the patients, as does selective destruction of pain fibers by radiofrequency heating or glycerol. Spinal posterior rhizotomy elicits in less than 4% a lasting dysesthesia entirely different in temporal sequence, locus, and type of pain: (a) it tends to be maximal early after operation and to improve, (b) the spontaneous pain is accompanied by severe allodynia, and (c) the pain is usually referred beyond the margins of the insentient (rhizotomized) zone and may even be referred to the corresponding area on the opposite side. Sindou's "selective posterior rhizotomy," i.e., cutting of the small fiber lateral component of each rootlet as it enters the cord, has not given rise to dysesthesias. These do occur briefly in 50% of the cases following spinal ganglionectomy, the sensations being referred to the dermatomal segment of the ganglion in question. The secondary afferent neurons in the mesencephalic, principal, oral, and interpolar nuclei for the trigeminal posterior roots have no counterpart in the spinal cord for the spinal posterior roots. We suggest that the explanation for the fact that neither trigeminal neuralgia nor trigeminal anesthesia dolorosa have a spinal clinical counterpart is related to the as yet unexplained special functions of the elaborate trigeminal secondary afferent neuronal apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)