Jack Phillips

Microdysgenesis in resected temporal neocortex Incidence and clinical significance in focal epilepsy

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (> 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslins (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p < 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Neuroendocrine dysfunction in the acute phase of traumatic brain injury.

background  Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post‐TBI period is unknown.

Topographical disorientation following unilateral temporal lobe lesions in humans.

Studies of the non-human temporal lobe, particularly the hippocampus, confirm its significant role in learning and memory, particularly allocentric spatial mapping of the environment. The role of the human temporal lobes in topographical orientation was investigated by examining the formation of representations of a large-scale real-world environment after unilateral left and right temporal lobe surgery. Patients and normal control subjects viewed videotape presentations of overlapping routes through a novel urban area. Topographical orientation was then assessed across a range of parameters. Right temporal lobe lesions alone gave rise to deficits in making proximity judgements. However, on all other topographical orientation tasks both right and left temporal lobe lesion groups were impaired relative to the normal control group, but the two patient groups did not differ significantly from each other. These findings suggest that such is the nature of remembering and way-finding in the environment that the integrity of both human temporal lobes is required.

The deamination of dopamine by human brain monoamine oxidase

SummaryThe deamination of dopamine has been studied in seven regions of human brain. Both A and B forms of the enzyme were found to be active towards this substrate. The ratio of activities of MAO-A: MAO-B was found to vary considerably from brain region to brain region, from about 1∶1 for the cerebral and cerebellar cortex to about 1∶2 for the pons and medula oblongata. Enzyme titration studies and comparisons of the substrate specificities of MAO-A and MAO-B across the brain indicated that dopamine was metabolised by the same MAO active centres as other monoamines. In the cerebral cortex, the Km values of MAO-A and-B towards dopamine were found to be 210 and 230 μM, respectively, indicating that the relative contributions of these two forms towards the oxidation of this substrate will not be significantly affected by changes in its concentration.

Patients' Aims for Epilepsy Surgery: Desires Beyond Seizure Freedom

Summary:  Purpose: To evaluate prospectively patients aims for epilepsy surgery as previously outlined theoretically by Taylor et al. (Epilepsia 1997;3:625–30).

Outcome Measurement after Vagal Nerve Stimulation Therapy: Proposal of a New Classification

Summary:  Purpose: Vagal nerve stimulation (VNS) is an adjunctive palliative therapy for refractory epilepsy. Effects of treatment are varied and some, such as the use of an external magnet for seizure termination, are unique to VNS. No accepted standard exists for outcome measurement after VNS treatment. We present a novel classification for outcome, which includes assessment of both seizure frequency and severity in VNS‐treated patients.

Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma

objective  In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.

Temporal neocorticectomy in management of intractable epilepsy : long-term outcome and predictive factors

Summary: We report the results of a long‐term follow‐up study of 50 patients who underwent removal of temporal neocortex with preservation of deeper limbic structures as surgical therapy for intractable temporal lobe epilepsy. The follow‐up period ranged from 3 to 15 years. Preoperative EEG investigations were based on interictal discharges alone. Three factors were predictive of a good outcome: (a) A clear unilateral anterior‐midtemporal focus (p < 0.01), (b) stereotypical onset of temporal lobe seizure (p < 0.005), and (c) greater volume of tissue removed at operation (p < 0.05). Overall results showed that 62% of patients experienced an outcome of “cure” or “almost cure,” as classified according to a modified version of Crandalls criteria (Crandalls I and II). Those who experienced a significant reduction in seizures but who continued to have intractable epilepsy (Crandalls III) were not considered to have had a good result. Overall outcome compares favorably with other that of centers using different surgical approaches and indicates that neocorticectomy is a suitable procedure in a highly selected population even when limited resources are available.

Hypopituitarism following traumatic brain injury (TBI)

Traumatic brain injury (TBI) is the commonest cause of death and disability in young adults living in industrialised countries. Recently, several studies have shown that hypopituitarism is a common complication of head trauma, with a prevalence of at least 25% among patients who were studied months or years following injury. This remarkably high frequency has changed the traditional concept of hypopituitarism being a rare complication of TBI, and suggests that most cases of posttraumatic hypopituitarism remain undiagnosed and untreated in clinical practice. It is therefore reasonable to infer that posttraumatic hypopituitarism may have an important contribution to the high physical and neuropsychiatric morbidity seen in patients with head injury. This article discusses the published reports on neuroendocrine dysfunction in TBI patients and the natural history of this disorder. The potential impact of posttraumatic hypopituitarism on recovery and rehabilitation after injury will also be examined, as well as the need for the identification, and appropriate and timely management of hormone deficiencies in order to reduce morbidity, aid recovery, and avoid the long-term complications of pituitary failure.

The oxidation of tryptamine by the two forms of monoamine oxidase in human tissues.

The selective monoamine oxidase inhibitors clorgyline and (-)-deprenyl have been used to determine the activities of monoamine oxidase-A and -B towards tryptamine in several human tissues. The results were compared with those obtained with the A-form-selective substrate 5-hydroxytryptamine, the B-form-selective substrate 2-phenethylamine and the common substrate tyramine. Tryptamine was found to be a substrate for both forms of the enzyme in human liver, kidney cortex and medulla and in seven different brain regions. The Km values of the two forms towards this substrate were similar in all the human tissues examined but the maximum velocities differed. Thus the A-form would contribute approximately 50% of the total monoamine oxidase activity towards this substrate in human cerebral cortex, whereas it would contribute about 60% in kidney cortex and medulla and 75% in liver. These results suggest that both forms of monoamine oxidase would contribute to the metabolism of tryptamine in human tissues and are difficult to reconcile with suggestions that tryptamine excretion may provide a simple index of monoamine oxidase-A inhibition.