Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review.

Chronic enteroviral meningoencephalitis is a well-recognized complication in patients with X-linked agammaglobulinemia (XLA). The majority of published cases refers to its occurrence in patients on no replacement therapy or on only intramuscular immunoglobulin. The advent of intravenous immunoglobulin (IVIg) in the early 1980s and its widespread use in XLA was thought to have virtually eradicated enteroviral meningoencephalitis in these patients. We describe the development of echovirus meningoencephalitis in an 11-year-old boy on regular IVIg replacement whose serum IgG levels were maintained at between 6 and 8 g/L (NR 6-13 g/L). Treatment with daily high-dose IVIg was commenced, with significant clinical improvement being noted within a few weeks in association with a reduction in blood-brain barrier permeability. The persistence of live virus, however, necessitated the use of intraventricular immunoglobulin. The virus proved resistant to two courses of specific intraventricular immunoglobulin and a 6-week course of oral ribavirin and eventually proved fatal 5 months after presentation. In view of the therapeutic uncertainties we have reviewed the use of immunoglobulin in the treatment of enteroviral meningoencephalitis over the past 6 years.

Five patients with Rasmussen's syndrome investigated by single-photon-emission computed tomography.

Five patients with Rasmussen's syndrome (sometimes known as smouldering encephalitis), are presented. This rare form of childhood epilepsy is characterized by intractable partial seizures with progressive neurological and mental impairment. Diagnostic brain biopsy shows the histological changes of active encephalitis, consistent with a viral infection. Although the raised cerebrospinal fluid (CSF) complement and interferon levels seen in some patients support this hypothesis, no infective agent has yet been isolated. All five patients were investigated by transmission computed tomography (CT) of the head, electroencephalography (EEG) and cerebral single-photon-emission computed tomography (SPECT) using 99Tcm-hexamethylpropylenamine oxime (HMPAO) and in addition 123I-amphetamine (IMP) in Patient 1. 99Tcm-HMPAO is now regarded as reflecting cerebral perfusion, whereas the uptake of 123I-amphetamine is more dependent on cell function. In all patients SPECT imaging demonstrated an area of hypoperfusion/hypometabolism which corresponded to the anatomical localization of the epiletogenic foci found by clinical assessment, EEG and CT. In all cases the SPECT study also demonstrated a more extensive area of abnormality than CT, and in the two patients who had sequential studies, alteration in the size of the defect was found which correlated with the patients' changing clinical condition. SPECT imaging in Rasmussen's syndrome may facilitate anatomical localization of the area of pathology, and may demonstrate a changing pattern in cerebral hypoperfusion/hypometabolism. It could also serve as a guide to accurate brain biopsy.

Problems in childhood migraine.

There are differences between childhood and adult migraine which justify clinical research. First, inessential differences, such as prominence of systemic upset, indicate need for clinical drug trials. Second, some paroxysmal phenomena of childhood such as paroxysmal torticollis, vertigo, and hemiplegia may be migraine precursors, and need therapeutic trials. Third, some proposed equivalents of migraine in childhood need study and definition, followed by clinical trials.

Headache and school absence.

The amount of time missed from school in two small town school populations was estimated by measuring absence from school and attendance at sickbay, and stated causes were analysed. School absence related to headache (expressed as percentage of pupil days missed out of possible pupil days, during two 12 week periods) in children aged 5 to 14 years, was 0.05%. This represented approximately 1% of all school absence, and was recorded (usually only once) in 3.7% of children. The duration of absence was one day or less on 85% of occasions. This low absence rate was in contrast with the high prevalence of headache reported by children aged 9 to 14 of between 76 and 94% according to age and sex. Attendance at school sick bay because of headache was recorded in 3.6% of children aged 5 to 19 (only 0.5% then left school early because of headache) in one 12 week period. It is concluded that although headache prevalence is high in the age groups studied, it is not a prominent cause of time missed from school.

Childhood mitochondrial myopathy with ophthalmoplegia.

A 14-year-old boy with mitochondrial myopathy is described, and the findings on muscle biopsy shown. He presented with mild weakness, and severe exercise intolerance; examination showed ptosis, external ophthalmoplegia and severe muscle wasting. There was a possible family history of a similar disorder. Metabolic study demonstrated severe lactic acidosis on exercise. Oxygen consumption was measured and found abnormally high at rest and on exercise. Biochemical study of extracted muscle mitochondria showed decreased respiratory rates with NAD-linked substrates. These and other results suggest the site of the defect to be in the electron transport chain. The possible significance of abnormally high oxygen consumption in the presence of such a defect is discussed.

Ponto-bulbar palsy with deafness (Brown-Vialetto-Van Laere syndrome).

The authors describe the clinical and electrophysiological features in 2 cases of ponto-bulbar palsy with deafness, and the clinical course and post-mortem findings in a sibling of one of these, who died in infancy, and who appears to have suffered from the same disease. The cases are compared with 17 previously published cases, and the disease is discussed in relation to other progressive neurological diseases of childhood.

Basilar migraine in childhood.

The incidence and different presentations of basilar migraine are described in a series of 132 children (80 boys, 52 girls) presenting with recurring headache considered to be migraine. Basilar migraine occurred in 29 children, and a further 18 had minor symptoms compatible with but not diagnostic of this form. The course was most often benign, with infrequent, fragmentary attacks and little disability. Rarely, attacks were both severe and frequent, but even then the clinical pattern and outcome usually followed a similar course. Only two children (with the youngest ages at onset) have serious disability, with mental slowing and (in one) permanent neurological sequelae. The relationship between basilar migraine and the syndrome of alternating hemiplegia of infancy is discussed. Because of the limited present knowledge, it is suggested that rigid definitions of migraine should be avoided.

Lipid abnormalities in untreated maturity-onset diabetics and the effect of treatment.

Plasma cholesterol and serum triglyceride levels and frequency of lipoprotein abnormalities were investigated in 126 untreated maturity-onset diabetics and 126 age- and sex-matched control subjects. Serum triglyceride levels were higher (mean: 1.67 mmol/l) and type IV hyperlipoproteinaemia occurred more frequently (16.7%) in the diabetic group as compared with the controls (1.29 mmol/l and 4.8% respectively). These findings were not explained by an excessive frequency of renal disease, hypertension or drug treatment amongst the diabetics. Normal men showed higher serum triglyceride (mean: 1.36 mmol/l) and lower plasma cholesterol (mean: 5.6 mmol/l) levels than normal women (1.21 mmol/l and 6.4 mmol/l respectively). No sex difference was seen amongst the diabetics. Triglyceride levels fell after one month of dietary treatment but only remained lowered in diabetics who required sulphonylureas for glycaemic control. After treatment for one year the correlation between serum triglycerides and blood glucose rose from r = 0.15 (NS) before treatment to r = 0.43 (p less than 0.001). Similarly the correlation between serum triglycerides and ponderal index rose from r = 0.19 (NS) to r = 0.28 (p less than 0.02).

Prospective comparison of modified fat-high-carbohydrate with standard low-carbohydrate dietary advice in the treatment of diabetes: one year follow-up study.

1. A prospective randomized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications. 2. During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate, modified-fat (MF) diet showed a similar decrease. 3. Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet. Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens. 4. Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America. A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose.

Migraine and reporoductive hormones throughout the menstrual cycle.

In a clinical survey the relation between migraine and menstruation was studied in 142 otherwise healthy women. In 24, onset of migraine coincided with the year of menarch. Of the 138 patients in whom onset of migraine predated the menopause, there were only 13 in whom attacks occurred regularly, and only, just before or during menstruation; in a further 11 attacks occurred regularly in relation to menstruation and at other times. Those with menstrually related migraine were more likely to have onset of migraine at menarche, to have associated weight gain and breast discomfort as part of a periodic syndrome, and to show improvement during pregnancy. There appeared no clear pattern of change at the menopause. In a study of reproductive hormones, blood was collected daily throughout a menstrual cycle from each of 8 women with menstrually related migraine, 6 with menstrually non-related migraine, and 8 healthy headache-free controls. Plasma levels of follicle-stimulating hormone (F.S.H.), luteinising hormone (L.H.), prolactin, oestrogen, and progesterone were measured in all. Plasma-testosterone was measured in 8 migraine patients. Mean plasma oestrogen and progesterone levels were significantly higher in migraine patients than controls for most of the menstrual cycle, with the most striking differences found in the late luteal phase for progesterone. No significant difference was found between the menstrually related and non-related patients for these or the other hormones measured. Mean plasma-prolactin levels were lower in migraine subjects than controls, but the difference was not significant. Mean plasma F.S.H. and L.H. levels were similar in both migraine and control groups. Plasma-testosterone levels were within the range for normal in the 8 migraine patients studied. No specific hormone changes were associated with the occurrence of a migraine attack, nor did rising or falling levels, or greater increments of change over given cycle phases, appear important in provoking attacks.