The past fifteen years has seen the classification of diverse substances into a group known as calcium antagonists (CAs). They have a common ability to reduce the transmembrane transport of extracellular calcium ions (CAe2+). This flow of calcium into vascular smooth muscle is ultimately associated with the development of tension and vasoconstriction. Some CAs appear to have a predilection for cerebral as opposed to systemic arteries and so may function as specific cerebral arterial vasodilators. It has been proposed that they might be useful in certain types of cerebral ischemia such as that due to arterial occlusion or prolonged vasoconstriction. Animal experiments and initial clinical trials give grounds for cautious optimism that CAs may become as useful in neurology as they have recently become in cardiology.

The problem of antiepileptic drug interactions is significant in that many epileptic patients are treated with multiple drug therapy. Moreover, patients may also be receiving additional medication for other concurrent disorders. Most drug interactions are pharmacokinetic, involving changes in absorption, protein binding, metabolism, or excretion. As a result, plasma levels of the antiepileptic drug may decrease leading to exacerbation of seizures. Alternatively, plasma levels may rise resulting in toxic side effects. Similar changes may also occur with drugs given for other disorders. In this paper, possible mechanisms of drug interactions are discussed. This is followed by a description of clinically significant interactions involving phenytoin, carbamazepine, barbiturates, valproic acid, benzodiazepines, and succinimides. Potentially serious drug interactions may be minimized by using as few medications as possible and by regularly monitoring plasma levels of antiepileptic drugs.

To investigate the neural generators of the subcortical somatosensory evoked potential (SEP) waves we studied the far-field SEPs in 20 normal adults. We stimulated the median nerve at the wrist and used a 40k gain, 25 msec sweep and a 150-3000 Hz bandpass. We recorded SEPs simultaneously over C3′ and C4′ using a non-cephalic clavicle reference. The following series of six positive waves were found reliably in all subjects: P9, PI 1, P13, P14, P16 and P17.

The P16 and P17 probably arise from the thalamus and/or thalamocortical projections. Recent evidence suggests that the thalamus is not a closed field and thus one should be able to find corresponding waveforms in far-field recordings. We believe that this is a function of the bandpass used and with the above paradigm these components can be reliably recorded.

We found significant ipsilateral and contralateral amplitude asymmetries beginning with the negative deflection after P14 and including P16 and P17. The amplitude was greater over the contralateral hemisphere. This suggested that both P13 and P14 are generated prior to decussation of the afferent fibres in the medial lemniscus. Bilateral recording allowed detection of this asymmetry which has not been previously reported as a means of determining the electrophysiological correlates of lateralization.

Andermann et al. described in 1972 an autosomal recessive inherited syndrome which associates agenesis of the corpus callosum, mental deficiency, and a peripheral motor deficit. We had the opportunity to study in detail 15 patients affected by this syndrome. As in the cases previously reported, the families of these children all originated from Charlevoix County and the Saguenay-Lac St-Jean area in the Province of Quebec.

Clinically, these patients have a characteristic facies and moderate mental retardation associated with a progressive motor neuropathy leading to loss of ambulation by adolescence and progressive scoliosis. In 13 of these 15 patients, neuroradiological investigation has shown either total or partial agenesis of the corpus callosum. In every patient in whom these tests were done, sensory nerve action potentials were absent and motor nerve conduction velocities reduced. We also found neurogenic abnormalities both on EMG and neuromuscular biopsies. These abnormalities are similar to those described in Friedreich’s ataxia and in hereditary motor and sensory neuropathy type II, although in our patients the motor deficit is much more severe than in these diseases.

The pathogenesis of the peripheral nervous system involvement is still unknown since there have so far been no autopsy studies of this syndrome.

Stenosis of the internal carotid artery reduces the flow velocity in the ophthalmic artery. Lowered velocity permits increased red cell aggregation and decreased red cell deformability which increases viscosity.

Contrary to the theory of remotely originating emboli, this is an alternate hypothesis regarding transient attacks of ocular and cerebral ischemia.

The ophthalmic artery circulation time was measured in two groups of patients. The circulation time was defined as the interval between the appearance of contrast media in the siphon of the internal carotid artery and in the ocular choroid. The measurement was made on 151 angiograms of 108 subjects. These vessels were normal. An additional 76 patients had 108 angiograms which showed various amounts of internal carotid artery stenosis. These 76 patients had transient ischemic attacks; retinal, cerebral, or both.

There is a significant difference in the ophthalmic artery circulation time in the two groups. The slowing in the ophthalmic artery is related to the degree of internal carotid artery narrowing.

The circulation time in a cerebral branch of the internal carotid was not measured. It is presumed that stenosis of the internal carotid artery would have the same effect on a cerebral artery as on the ophthalmic artery.

In an attempt to find the best electrophysiological indicator of improvement for the neuropathy present in patients with chronic renal failure undergoing hemodialysis, several types of nerve conduction were studied at the beginning of dialysis and six months later. Sural nerve conduction and late response latencies were recorded in addition to conventional motor and sensory nerve conductions. After six months of hemodialysis, sensory nerve conduction velocities in the median, ulnar and sural nerves were improved. These values appear to be the most sensitive indices of the beneficial effect of hemodialysis on the neuropathy.

The relationship between the segmented EMG activity in flexor carpi radialis evoked by imposed angular wrist displacement was studied with respect to the level of pre-existing background activity in 30 normal human subjects. Input-output response planes demonstrate that the magnitude of the Ml & M2-3 segments is dependent on both the displacement parameters and the level of pre-existing EMG activity in the stretched muscle. If the level of background activity exceeded 4-5% of the maximum voluntary contraction, the onset latency of the M1 segment and duration of the Ml and the M2-3 segments remained constant (within ± 2 msec) for different magnitudes of step load displacements, despite marked variation in the range of the displacement’s amplitude, duration, velocity, and acceleration. We propose that the dependency of the relationship between reflex magnitude and imposed movement parameters on tonic motoneuron activity, as represented by pre-existing EMG levels, may reflect an automatic adjustment mechanism that could be utilized in servo compensation of movements requiring markedly different force levels.

The amplitude and temporal modulation of the segmented EMG activity in flexor carpi radialis, evoked by imposed angular wrist extension, was studied with respect to the level of pre-existing background activity in rigid parkinsonian (PK) and dystonia musculorum deformans (DMD) patients. The interdependence of the evoked M1 and M2-3 segments on pre-existing background EMG activity and initial velocity of imposed displacement was established previously for a normal population. Individual responses of 21 parkinsonian and 12 dystonic patients were compared to the established normal “response volume”. The augmented magnitude of the M2-3 segment in rigid PK patients, which correlates to the measure of rigidity, could not be accounted for by the low level of pre-existing EMG activity. Therefore, increased descending facilitation does not impinge directly on alpha motoneurons. Paradoxical excitation in the shortened muscle and resetting of tonic tremor of the stretched muscle by the imposed wrist extension are two other demonstrated abnormalities which may also contribute to PK rigidity. In contrast, DMD patients demonstrated normal amplitude modulation of the M1 and M2-3 segments, but exhibited a disturbance of normal temporal mechanisms that result in constant duration of the M1 and M2-3 responses with imposed force step loads.

The segmented EMG activity in flexor carpi radialis to imposed wrist movements was studied in 18 hemiplegic subjects with vascular lesions of the sensorimotor cortex or internal capsule and compared to that in age-matched normal subjects. The segmented EMG activity in the stretched muscle was normalized against the maximum M response elicited by electrical stimulation of its peripheral nerve in hemiplegic and normal subjects. This M response was used to estimate the maximal activity of the motoneuron pool. Twelve of the hemiplegic patients showed a stereotyped abnormal segmentation pattern of the EMG activity characterized by: an increased M1 segment of prolonged duration with both an increased sensitivity to low initial velocities of displacement and an increased slope of the input-output relationship for the range of velocities tested; absent or diminished activity during the interval of the normal M2-3 segment; and a late component not evident in normal subjects. The increased magnitude of the EMG activity during the MI interval, markedly exceeded the normal range of control values. A method to demonstrate the response distribution of the interrelationship of the magnitude of the M1 segment using two variables (background EMG activity and initial velocity) for individual responses rather than average responses is presented. The results of the study indicate that: the increased excitability, reflected in the enhanced EMG over the M1 segment does not result from increased levels of resting alpha motoneuron activity and may result from disruption of polysynaptic internuncial influences on alpha motoneurons; the absent or diminished activity over the interval of the normal M2-3 segment may partially result from the interruption of a transcortical reflex by the vascular lesions.

Retrograde amnesia was assessed in demented and non-demented Parkinson’s patients using a test of remote memory spanning the years from 1920-1979. Results indicated that the demented patients 1) scored significantly below normal controls and 2) had equal impairment for all time periods. This pattern was like that seen in other dementing illnesses (i.e., Huntington’s and Alzheimer’s diseases), but different from that in amnesic disorders, such as Korsakoff s syndrome. The data, therefore, suggest qualitative differences in pattern of remote memory loss between the dementias and amnesic syndromes.

This retrospective study documents the experience of two large Canadian teaching hospitals with occlusive cerebrovascular disease in young adults. Chart review disclosed 76 patients aged 15-40 years during a recent six year period. An apparent cause, or significant coincident risk factors were found in 51 patients (67%). The most prevalent recognized causes were atherosclerosis, emboli from cardiac sources or intracranial aneurysms, and complicated migraine. Pregnancies or use of oral contraceptives were apparent coincident risk factors.

The clinical and neuropathological findings in two infants with congenital nemaline myopathy are described. One patient presented at birth with severe hypotonia, respiratory failure and contractures and died shortly after the neonatal period. The other presented at age two months with hypotonia and, following a period of clinical stability, died at age seven months from respiratory failure. Pathological findings in the fatal neonatal case revealed numerous rod bodies in lingual, pharyngeal, diaphragm and limb muscles, correlating with clinical findings. Significant, but less rod body involvement was found in the diaphragm and limb muscles of the second patient. Although a neural basis has been suggested for this disorder, no abnormalities were found in the central nervous system or in the peripheral nerves of these two severely affected patients.

The diagnosis of extracranial metastases from a pituitary tumor was confirmed by the use of the immunoperoxidase technique. This is believed to be the first case of carcinoma of the pituitary gland with bony metastases where the diagnosis has been confirmed in that manner.