Second edition

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changes tend to occur very gradually, with roughly the
same time course as the late-delayed radiation encephalopathy;
hypothyroidism is especially important to keep
in mind as it may present as a dementia. Hypothalamic
damage may also cause other symptomatology, as in one
case of hyperphagia with severe weight gain (Christianson
et al. 1994).
Course
This is as described above.
Etiology
As indicated above, the acute form occurs secondary to a
radiation-induced breakdown of the blood–brain barrier.
The early-delayed type represents demyelinization
(Lampert and Davies 1964), which probably occurs secondary
to radiation damage of oligodendroglia. The half-life of
myelin ranges from 5 to 8 weeks and, with loss or dysfunction
of oligodendroglia, symptoms appear as myelin
degrades in the absence of ongoing replacement. With a
new ‘crop’ of oligodendroglia, replenishment of myelin
gradually occurs and symptoms resolve.
Late-delayed radiation encephalopathy probably occurs
on the basis of hyalinization of penetrating arterioles with
fibrinoid necrosis, microthrombosis, and a myriad of
microinfarctions (De Reuck and vander Eecken 1975;
Pennybaker and Russell 1948).
Differential diagnosis
The history of irradiation makes the diagnosis of the acute
form obvious and is highly suggestive when the delayed
forms present after whole-brain irradiation with delirium
(in the case of the early-delayed form) or dementia (with
the late-delayed form). Difficulties may arise, however,
when the delayed forms occur after focal irradiation for a
central nervous system tumor, as in these cases the possibility
exists that the focal findings could represent not radiation
damage but rather tumor recurrence. In such cases,
although MR scanning may not be helpful, positron emission
tomography (PET) scanning reliably distinguishes the
two possibilities, demonstrating decreased glucose utilization
in radiation encephalopathy and increased utilization
in cases of tumor recurrence (Glantz et al. 1991).
Two other differential possibilities to keep in mind are
the appearance of a new tumor and large-vessel infarction.
Irradiation may cause tumors (Robinson 1978) and,
although this is rare, both meningiomas (Brada et al. 1992;
Soffer et al. 1983) and gliomas (Zampieri et al. 1989) may
appear. Further, in cases in which large vessels were exposed
to irradiation, a vasculitis may occur, with thrombosis and
large, territorial infarctions (Grattan-Smith et al. 1992).
Treatment
References 459
Acute radiation encephalopathy may be treated with
steroids and, indeed, it is customary to give steroids
prophylactically.
Early-delayed radiation encephalopathy may show some
response to either dexamethasone or prednisone; the symptomatic
treatment of delirium is discussed in Section 5.3.
Treatment of the late-delayed form of radiation
encephalopathy is not settled: a large case series suggests
improvement with either heparin or warfarin (Glantz et al.
1994). The symptomatic treatment of dementia is discussed
in Section 5.1.
REFERENCES
Adams JH, Graham DI, Murray LS et al. Diffuse axonal injury due
to non-missile injury in humans: an analysis of 45 cases. Ann
Neurol 1982; 12:557–63.
Adams JH, Doyle D, Ford I et al. Diffuse axonal injury in head
injury: definition, diagnosis and grading. Histopathology 1989;
15:49–59.
Agha A, Sherlock M, Brennan S et al. Hypothalamic-pituitary
dysfunction after irradiation of nonpituitary brain tumors in
adults. J Clin Endocrinol Metabol 2005; 90:6355–60.
Annegers JF, Hauser WA, Coan SP et al. A population-based study
of seizures after traumatic brain injury. N Engl J Med 1998;
338:20–4.
Arieff AJ, Wetzel N. Subdural hematoma following epileptic
convulsion. Neurology 1964; 14:731–2.
Bigler Ed. Neuropsychological results and neuropathological
findings at autopsy in a case of mild traumatic brain injury.
J Int Neuropsychol Soc 2004; 10:794–806.
Black DW. Mental changes resulting from subdural hematoma.
Br J Psychiatry 1984; 145:200–3.
Blumbergs PC, Jones NR, North JB. Diffuse axonal injury in head
trauma. J Neurol Neurosurg Psychiatry 1989; 52;838–41.
Brada M, Ford D, Ashley S et al. Risk of second brain tumor after
conservative surgery and radiotherapy for pituitary adenoma.
BMJ 1992; 304:1343–6.
Cameron MM. Chronic subdural hematoma: a review of 114
cases. J Neurol Neurosurg Psychiatry 1978; 41:834–9.
Christianson SA, Neppe V, Hofman H. Amnesia and vegetative
abnormalities after irradiation treatment: a case study. Acta
Neurol Scand 1994; 90:360–6.
Constine LS, Woolf PD, Cann D et al. Hypothalamic-pituitary
dysfunction after radiation for brain tumors. N Engl J Med
1993; 328:87–94.
Corsellis JAN. Boxing and the brain. BMJ 1989; 298:105–9.
Corsellis JAN, Bruton CJ, Freeman-Browne D. The aftermath of
boxing. Psychol Med 1973; 3:270–303.
Critchley M. Medical aspects of boxing particularly from a
neurological standpoint. BMJ 1957; 1:357–66.
Crompton MR, Layton DD. Delayed radionecrosis of the brain
following therapeutic X-irradiation of the pituitary. Brain
1961; 84:85–101.