We have examined the distribution of HLA antigens in 70 multiple sclerosis (MS) patients divided in three groups defined according to clinical criteria: benign MS, severe MS, cerebellar MS. We have found a significant association between severe MS and HLA-DR2, and between benign MS of more than 15 years of evolution and HLA-DR3. We review previous work along the same line and conclude that the association of HLA antigens with “clinical subgroups of MS” could indicate a genetically based heterogeneity of the disease and offer help in establishing a prognosis.

We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5%unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects.

Treatment planning for patients with tumours of the skull requires a true multidisciplinary approach. Super-selective angiography, using a protocol approach, is necessary in building a proper strategy plan for treatment of these lesions. Embolization done by a well trained team has proven to be a valuable adjunct to the various treatment methods and it may eliminate the need for radiation of benign lesions of the base of the skull.

Dystonic torticollis has been treated with local injections of botulinum toxin in a single blind study of 12 patients. A significant decrease of abnormal movements was recorded, and pain improved. Further studies are desirable to define the optimum dosage and site for injections, and the long term effects of repeated injections.

High resolution ultrasound has been used intraoperatively on forty-five patients with various intracranial lesions. The technique is quickly and easily carried out under sterile conditions in the operating room. Successful localization of both primary and metastatic tumors of various sizes, depths and consistencies have been made prior to extirpation or biopsy. Several of the biopsies were done through small burr holes. Arteriovenous malformations, abscesses, bone fragments from trauma, gliotic epileptic foci and ventricles for shunt placement have been readily found. No significant complications have been encountered. A new technique for localizing superficial lesions is described. An overall reduction in operating time and unnecessary trauma to the patient has resulted from more accurate intraoperative localization of intracranial lesions with real time ultrasound.

A review of patients with epilepsy showed that 5.9% had seizures exclusively in sleep (ES) and 4.7% had seizures predominantly but not exclusively in sleep (PS). These groups were compared with a group (W) with seizures mainly in wakefulness. The following significant differences were obtained: 1) generalized convulsions predominated in the ES while partial seizures were more common among PS and W patients, 2) seizures occurred less frequently in the ES group, and 3) more W patients had EEGs with generalized epileptiform activity and positive family histories for epilepsy.

We suggest the lower frequency of seizures in the ES group and the declining prevalence of sleep epilepsy are due to: 1) the high proportion of generalized as opposed to partial seizures in sleep and 2) more effective control of generalized seizures compared to partial seizures by modern anti-epileptic drug management.

The author describes four different approaches to clival tumours, and reviews his experience with 33 chordomas of the clivus. He also reviews his large experience with tumours invading the floor of the anterior and middle cranial fossae, and describes various surgical approaches for the removal of these tumours, followed by reconstruction of the bony floor with bone grafts, and dural reconstruction.

The management of pineal region tumors has changed considerably since the introduction of microsurgery and CT scanning. Analysis of our own series of 36 patients, comparing those treated in the pre-CT scan and microsurgery era with those treated afterwards, shows the important role these two techniques play. Current controversies in treatment and our own approach to management of pineal region tumors are discussed.

Does the human fetal brain influence muscle development? The importance of suprasegmental cerebral influence on developing human fetal muscle is less well understood than the control of histochemical differentiation of muscle by the motor neuron. Muscle biopsies of 21 hypotonic infants and children with nonprogressive congenital lesions of the cerebellum and/or brainstem were studied by histochemical methods. Two neonates who died with severely dysplastic brains and no descending motor tracts had normal muscle. The others, particularly those with cerebellar hypoplasia, had delayed muscle maturation, selective predominance of type I or II muscle fibres or disproportion in fibre sizes. It is concluded that the motor unit is capable of developing normally without suprasegmental influence, but that an abnormal balance of descending impulses may alter histochemical differentiation of fetal muscle. The small ‘subcorticospinal’ pathways arising in the brainstem probably are more influential than the larger corticospinal tract because of later myelination in the latter. The muscle biopsy thus serves to provide evidence of suprasegmental disease in infantile hypotonia.

We report the case of a patient with idiopathic aqueductal stenosis and hydrocephalus who had several episodes of akinetic mutism, each preceded by shunt malfunction, that resolved with shunt revision. She also developed a parkinson’s syndrome resistant to shunt revision but responsive to antiparkinsonian medications. The Parkinson’s syndrome and the episodes of akinetic mutism may be related to a reduction of dopaminergic input to the striatum and to the cingulate and frontal cortex brought about or worsened by ventricular dilatation.

A review has been carried out of those patients with a craniopharyngioma who were treated initially in our institution and had a microsurgical excision of their tumour during the period of time when newer and sophisticated modalities of investigation and treatment were available. Twenty-nine patients with craniopharyngioma were treated initially by microsurgical excision of their tumour at the Hospital for Sick Children from January 1976 to June 1985. In 21 a total removal of the tumour was performed, and there has been no clinical evidence of recurrence. No deaths were recorded in any of the 29 patients. The principal morbidity has resulted from endocrine deficits that these patients exhibit.

This paper describes four patients with thoracic spinal lesions in whom the initial clinical presentation was highlighted by complaints in the lower back and lower extremities, in the absence of thoracic spinal or radicular symptoms. Initial myelography, confined to the lumbar region, failed to reveal a cause for the patients’ symptoms. Subsequently, diagnostic consideration of a thoracic spinal lesion prompted repeat myelography of the thoracic region which demonstrated a relevant lesion in each case. It is important to visualize the thoracic cord when myelography is performed for the investigation of pain or neurological symptoms in the lower back or lower extremities.

Twenty patients with chronically progressive multiple sclerosis (MS) were randomised in a double-blind controlled study to assess the efficacy of plasma exchange therapy. All patients were immunosuppressed with prednisone and azathioprine and underwent either plasma exchange or sham apheresis. The 10 patients in each group were similar in age, sex, duration of disease and degree of disability. Clinical and laboratory responses were assessed immediately following the course of exchange or sham therapy, and 3 to 6 months later, by individuals blinded to the type of therapy administered. Although modest improvement was suggested on clinical examination in 7 of 10 patients exchanged and 3 of the 10 sham treated group, this was transient and was not accompanied by any change in disability status scores. No differences in abnormal laboratory investigations were demonstrable between the two patient groups following therapy. We conclude that plasma exchange therapy using this protocol is unlikely to be of clinical benefit as an adjunct in the management of chronically progressive M.S.

A 27-year-old woman presented with hemotomyelia during pregnancy. Needle drainage of the spinal cord was followed by relief of symptoms. Symptoms recurred during a second pregnancy 4 years later and she presented with an avascular mass in the midcervical spinal cord. This lesion proved to be hemangioma calcificans, a densely calcified and ossified variant of cavernous angioma.

Early hemorrhagic changes in the spinal cord were compared in three experimental spinal cord injury models in the rat in order to determine the nature and consistency of spinal cord hemorrhage following specific and quantitated forces of injury. The spinal cords were injured by weight-dropping, aneurysm clip and extradural balloon compression techniques. Hemorrhagic changes were assessed quantitatively by the image analyser at 1 and 3 hours after injury. Tissue damage was assessed by determining the percentage of total cross sectional area containing hemorrhage. The extent of hemorrhage at site of injury in the clip and balloon preparations was equal, but several times lower in the weight-drop induced injury. Within each experimental group no appreciable differences were observed at the site of injury between the 1 and 3 hours preparations. The variability of damage within experimental groups was most in the weight-dropping and balloon and least in the clip preparations. Differences were also indicated with respect to the distribution of hemorrhage in grey versus white matter. These findings may be of significance when functional recovery is considered in various experimental acute spinal cord injury models.

The role of the carotid siphon as a source of embolic material has had limited morphological or clinical study. The morphologic data available suggests that the siphon plays only a small role in embolic cerebrovascular disease. Clinical studies, however, suggest that it has a significant ischemic potential. To clarify this apparent discrepancy, we have designed a scanning electron microscope study of the carotid siphon. Eighty percent of the specimens from the carotid bifurcation and 30% of the siphon specimens showed evidence of damaged endothelium with attached red cell and platelet debris. The embolic potential of the siphon is estimated to be between ⅓ to ½ that of the carotid bifurcation. This supports the most recent clinical studies.

Two patients are reported with hemiballismus due to lesions in the striatum as documented on CT scan. The involuntary movements persisted for one and five years respectively. A third patient with more typical self-limited hemiballismus had no evidence of a causative lesion on CT scan. It is proposed that lesions outside the subthalamic nucleus of Luys may interfere with the compensatory mechanisms which can result in the spontaneous resolution of hemiballistic movements. None of the patients benefited from the use of sodium valproate therapy, however, pimozide reduced the severity of the dyskinesia in the two with longstanding hemiballismus.

This paper reviews the author's personal experience with the management of 204 patients with the clinical diagnosis of acoustic neuroma. Craniotomy was performed in 181 of these cases, all of whom were proven to have acoustic neuromas. The remaining 23 cases with the clinical diagnosis of acoustic neuroma did not have tumour surgery, mainly because of advanced age or concurrent disease, although some required shunts for hydrocephalus. The management of acoustic neuromas including the selection of surgical approach depends upon the patient's age and general health, the size and growth direction of the tumour, previous surgical attempts at removal, and the presence of hydrocephalus, a contralateral tumour, and serviceable hearing. Twenty-nine other cases with the clinical diagnosis of acoustic neuroma underwent craniotomy: 20 had petrous or tentorial meningiomas encroaching on the porus acousticus or growing in the internal auditory canal, six had neuromas of the seventh cranial nerve and three had arachnoiditis occluding the internal auditory canal.

Cough syncope is a more common complication of childhood asthma than formerly recognized. We report twelve children with typical cough syncope who were identified in a pediatric clinic over a period spanning seven years. The condition may be confused with epilepsy because of frequently associated brief clonic convulsive movements during the height of the cerebral anoxia. Cough syncope is readily distinguished from epilepsy by a thorough history. The management and prevention of cough syncope is directed at the aggressive control of bronchospasm in children with asthma.