In 1971, Andermann and Andermann described an autosomal recessive syndrome found within the Charlevoix and the Saguenay populations (Quebec, Canada) characterized by agenesis of the corpus callosum (ACC) associated with motor and sensory neuropathy, mental retardation and dysmorphic features. A study of CT in 64 patients demonstrated a total ACC in 37 cases (57.8%), partial ACC in 6 cases (9.4%) and the presence of the corpus callosum in 21 cases (32.8%). The latter was confirmed by MRI in 3 cases. CT of patients without ACC revealed a high frequency of developmental or degenerative midline anomalies, particularly interhemispheric fissure enlargement and posterior fossa atrophy. The clinical presentation and the natural course of the neuropathy, the intellectual impairment and the behavioural manifestations are identical amongst individuals with or without ACC. Individuals with or without ACC are found within the same family and often within the same sibship. These observations support the hypothesis of a single genetic syndrome in which the constant manifestation is the motor and sensory neuropathy.

Vastus lateralis muscle biopsies of four unrelated male neonates showing myotubular (i.e. centronuclear) myopathy (MM) were compared with muscle from four human fetuses in the myotubular stage of development, a 31 week preterm infant and four term neonates. The perimysium, blood vessels, spindles, myelinated intramuscular nerves, and motor end-plates in MM are as well developed as in term neonatal muscle. The cytoarchitecture of myofibres in MM is more mature than that of fetal myotubes in the spacing of central nuclei, Z-band registry, development of the sarcotubular system, and in the condensation of nuclear chromatin and nucleoli. Triads in MM may retain an immature oblique or longitudinal orientation. Myofibrillar ATPase shows normal differentiation of fibre types, consistent with nonnal innervation. Spinal motor neurons are nonnal in number and in RNA fluorescence. Immunoreactivity for vimentin and desmin in myofibres of MM is uniformly strong, as in fetal myotubes and unlike mature neonatal muscle. Maternal muscle biopsies of two cases also showed scattered small centronuclear myofibres reactive for vimentin and desmin. The arrest in morphogenesis of fibre architecture in MM is not a general arrest in muscle development. Persistence of fetal cytoskeletal proteins that preserve the immature central positions of nuclei and mitochondria may be important in pathogenesis. Vimentin/desmin studies of the infant and maternal muscle biopsies are useful in establishing the diagnosis.

Weakness of distal muscles of one upper limb which progresses over 1 year and then appears to arrest (“monomelic amyotrophy”) has been reported mainly in Japan and India. We report 5 cases of a similar syndrome occurring in Canada. In our cases the wasting affected the forearm muscles of one upper limb (sparing brachioradialis and extensor carpi radialis). There was minimal wasting and electromyographic changes in the opposite upper limb. The CT myelogram showed unilateral wasting of the cervical cord.

Normal pituitaries, pituitaries showing CHC and selected adenomas were assessed for their possible content of intermediate filaments (IF), using immunohistochemical techniques. Normal pituitaries were stained for each of the five known IF (Cytokeratins (CK), glial fibrillary acidic protein (GFAP), desmin, vimentin, and neurofilaments (NF)). Desmin could not be demonstrated, and NF staining was limited to processes in the posterior gland. In serial sections, CK was demonstrated in some corticotrophs, somatotrophs, and lactotrophs. Vimentin was limited to processes in the posterior gland. Folliculo-stellate cells (FSC), demonstrated by staining for SlOO protein, exhibited a small subpopulation staining for CK, and another subpopulation staining for GFAP. GFAP was also demonstrated in glial processes in the posterior gland. Cells showing Crooke's hyaline change stained intensely for CK. Null cell adenomas did not stain for CK. Corticotroph adenomas, somatotroph adenomas, with or without fibrous bodies, and lactotroph adenomas contain CK-immunoreactive cells. We conclude that CK is the major IF present in the anterior pituitary gland, within some normal corticotrophs, somatotrophs and lactotrophs, and also in adenomas derived from these cells.

A patient with tardive dyskinesia dominated by pelvic thrusting movements is described. A retrospective review of the clinical features documented in patients with metoclopramide- and antipsychotic-induced tardive dyskinesias seen over a six year period demonstrated that the occurrence of pronounced pelvic thrusting and respiratory dyskinesias were significantly more common in the metoclopramide treated group. The occurrence of bucco-linguomasticatory movements, limb stereotypies or chorea, and mild truncal or abdominal rocking were not significantly different between the two groups. None of the tardive dystonia patients had metoclopramide as the causative agent. These findings will require confirmation in larger, better matched patient populations. Whether the differences relate to different pharmacologic profiles of drug action, patient populations exposed, or other factors, remains to be elucidated.

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.

The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders which is associated with more or less degrees of cerebral involvement. There are four separate entities within CMD nosology. Among these Fukuyama's CMD (FCMD) is highly prevalent in Japan, whereas the classic form with normal or subnormal intelligence, also known as the occidental type, covers the vast majority of cases in the West. We report a case of FCMD seen in a Turkish child.

Isolated angiitis of the central nervous system, a rare inflammatory condition of the nervous system, characterized by vasculitis of the small vessels, has not, to the best of our knowledge, been described in childhood. It usually presents with a diversity of neurological symptoms in the fifth to eighth decades of life. We reviewed the case of an 8 year old male with autopsy proven isolated cerebral angiitis, to encourage the consideration of this disorder in children; and to emphasize the lack of sensitivity of present modalities of neurological investigation in the diagnosis.

This is a review of reserpine, haloperidol, and various phenothiazines that produce parkinsonism and other movement disorders. The by-products of illicit meperidine synthesis, MPTP and its more sinister companion, MPP, are also discussed. Movement disorders, transient or fixed, frank parkinsonism and/or dyskinesia, due to a variety of other medications and toxic agents are included. These are methanol, lithium, methyldopa, antimetabolites, antidepressants, sympathomimetic anorexiants, some types of antihistamines, and various combinations of agricultural chemicals.

That non-rheumatic atrial fibrillation is an independent risk factor for cerebral infarction has not been established with certainty. The rationale underlying contemporary clinical trials of warfarin therapy for the prevention of stroke in patients who have non-rheumatic atrial fibrillation is that the majority of strokes in such patients are due to cardiogenic cerebral embolism. However, there is evidence to suggest that the increased probability of stroke attributed to this arrhythmia is due to its association with other risk factors such as hypertension, diabetes mellitus, and atherosclerosis. The question of who should be anticoagulated is a major public health issue since atrial fibrillation is present in approximately ten per cent of the general population aged 65 or more years.

Next to acoustic neuromas, meningiomas are the most common benign tumour of the posterior fossa. This paper reviews the personal experience of one of the authors with the management of 26 posterior fossa meningiomas and 212 acoustic neuromas. The aim was to compare the clinical and radiological features of these two types of posterior fossa tumours to determine whether they can be differentiated preoperatively. The study also aimed at analysing the surgical treatment of posterior fossa meningiomas. The results showed that posterior fossa meningiomas can usually be differentiated from acoustic neuromas on the basis of clinical and radiological features. Preoperative differentiation aids surgical management, especially for selection of surgical approach. In most instances, posterior fossa meningiomas can be totally resected with minimal morbidity and mortality.

An understanding of the mechanisms responsible for tumor-associated edema involves the elucidation of the role played by a number of intra-related processes. These include (i) the permeability of new tumor microvessels that are associated with tumor angiogenesis; (ii) alterations in microvascular permeability due to factors secreted by tumor cells; (iii) immunological mechanisms and (iv) increased microvessel permeability associated with inflammation. The rationale for a role for inflammatory processes in tumor-associated edema has been outlined and the role of non-steroidal anti-inflammatory drugs in modulating experimental and human tumor-associated edema has been explored.

Magnetic Resonance Imaging (MR) and Computer Assisted Tomography (CT) guided stereotaxis combined with intraoperative impedance monitoring and multiple sequential biopsies provides the opportunity to correlate the results of radiologic imaging with impedance and histopathology. The authors present the methods used and preliminary results obtained from 30 stereotactic biopsies with complete correlation in 12 cases. Impedance changes correlate accurately with lesion margins as defined by histology. CT images of enhancing lesions correlate quite closely to the histopathologic lesion margins whereas the appearance of the lesion on MR images is often larger than subsequently identified by either impedance or at pathologic examination. Impedance monitoring is a useful adjunct to stereotactic biopsy as it helps to accurately define lesion margins and can help direct the choice of biopsy sites.

The Ommaya Reservoir plays an important role in a select group of neuro-oncology patients with meningeal malignancy. The benefits derived must be balanced against potential complications associated with insertion and use of the apparatus. Side effects may be minimized by careful attention to patient selection, pre-operative CAT scan (or MRI), precise surgical technique, perioperative prophylactic antibiotics and meticulous procedure during use of the reservoir.

Fifty patients with malignant supratentorial tumours were treated with intra-operative photodynamic therapy (PDT); in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in 5 cases a solitary cerebral metastasis. All patients received a porphyrin photosensitizer 18-24 hours pre-operatively. Photoillumination was carried out at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The light energy density ranged from 8 to 175 J/cm2. In 8 patients additional interstitial light was administered. The operative mortality was 4%. Follow up has ranged from 1 to 30 months. The median survival for the 45 primary malignant tumours was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, respectively. In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (eg. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases who did not have a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively. Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.

The management of patients with supratentorial malignant astrocytomas has remained a major problem. Patients continue to die from a lack of local control in 90% of cases despite an improvement of median survival seen with the use of postoperative radiation therapy. Because of this, there has been considerable interest in exploring novel ways of possibly improving results. This paper reviews the rationale and clinical results with the use of altered fractionation schemes, brachytherapy, radiation sensitizers, hyperthermia, particle therapy, and radiosurgery in the treatment of these patients. Currently, there is no demonstrated advantage with the use of these experimental modalities in the initial management of patients. There would appear to be some benefit for selected patients who are treated with brachytherapy at recurrence, but its efficacy as part of initial management remains to be determined in ongoing randomized prospective trials.