Performance on an eye-hand tracking task and a multi-joint reaching movement to a visual target was studied in a patient with stable cerebellar ataxia and in control subjects. The patient subsequently died and a full neuropathological examination was performed. The neuropathological findings were similar to those seen in patients with paraneoplastic cerebellar degeneration, but no tumor was found at autopsy eight years after onset of the patient's cerebellar syndrome. A severe cerebellar cortical degeneration with complete Purkinje cell loss was demonstrated, whereas cerebellar nuclei and brainstem structures showed no neuronal loss. Tracking performance by the patient was characterized by abnormally large numbers of high velocity movements and hand direction reversals, and by excessive lagging of the hand behind the target in time. In the multi-joint reaching movement, the patient showed a delay in movement onset at the elbow joint compared to movement onset at the shoulder joint. The velocity profile of the movement at the shoulder joint was abnormal. The duration of the acceleration phase was poorly correlated with both peak angular velocity and the duration of the deceleration phase. One of the most striking findings was the inability of the patient to consistently produce the same movement direction from trial to trial while reaching to the same target. Our data suggests that the cerebellar cortex is involved in multiple aspects of motor control including visuomotor integration mechanisms.

Electroencephalographic and neuro-imaging data were correlated with the lobe of cortical resective surgery among 48 patients age 16 years or less with medically intractable partial seizures. Decisions about surgery were determined by clinical judgement and therefore our results reflect the weight of these factors in clinical practise. Neuroimaging disclosed a lesion over the operated lobe in 32 patients (67%). Multiple EEGs demonstrated a most active spike focus over the operated lobe in 32 patients (67%). Although only 34 patients had a recorded seizure, this clearly arose over the operated lobe in 23 (68% of the 34 patients; 48% of series). Persistent focal delta activity appeared in 20 of the 48 patients (42%). No instance was encountered in which false lateralization of regional or focal interictal EEG spikes or delta when normal apiculate phenomena were excluded. Thus, the scalp EEG remains a valuable guide to epileptogenesis, even among young patients, and should continue to play a major role in determining the region of cortical resection. Effectiveness of cortical resection for seizure control was clearly better among patients with a single major lesion and among those with normal intelligence.

Two additional patterns, minuscule 28 per second positive spikes and huge N-shape potentials, have been identified exclusively in the EEGs of patients with 14 and 6 per second positive spikes. They occur predominantly during drowsiness and light sleep, usually in children, seldom in young adults. Their presence adds little to the clinical relevance of positive spikes. Familiarization with the N-shape potentials — the commoner of the two patterns — is important, lest they are mistaken for interictal abnormalities of significance such as atypical spike-wave complexes.

Epileptic seizures of focal origin often occur unpredictably as do interictal spikes. It is often assumed that spikes increase prior to seizures of focal origin and that antiepileptic medication affects spikes and seizures in a parallel fashion. We review evidence that this assumption is invalid and that there is a clear dissociation between spikes and seizures: increases in spiking before seizures have not been clearly documented; decreases in antiepileptic medication do not result directly in increased spiking; seizures are often followed by long-lasting increases in spiking; finally, seizures are no more likely when spikes are frequent than when spikes are rare. It therefore appears that spikes and seizures are two quite distinct phenomena, both originating in the epileptic focus but varying over time differently from what is most often believed.

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.

220 patients with isolated and idiopathic spasmodic torticollis were followed and treated over a 14 year period. Each patient was given a short questionnaire leading to the present retrospective data analysis. In most areas, including female preponderance and frequency of postural tremor, the findings confirmed previous studies and highlighted particular points: importance of psychopathological antecedents and association with stressful life-events. The discussion deals with some of the conflicting debates surrounding this unusual disorder. What is the role of psychopathological factors? What is the therapeutic prognosis? The best therapeutic results were obtained by combining anticholinergic drugs, local injections and rehabilitation.

This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antogonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.

Neurodegenerative diseases are characterized by selective degeneration of certain biochemically distinct subpopulations of central neurons. Studies of the intrinsic vulnerability of such neurons to injury by excitatory amino acids in vitro, as well as study of neurologic syndromes produced in animals or humans by ingestion of environmental excitatory amino acid neurotoxins may suggest a link between excitotoxicity, and the pathogenesis of certain neurodegenerative diseases.

In a consecutive series of 40 patients selected by EEG studies for surgical treatment of temporal lobe seizures, magnetic resonance imaging showed structural lesions in 25% and signal abnormalities, usually in the mesial temporal region, in another 35%. Pathological changes included structural lesions in over 30% of patients and sclerosis of the amygdala in almost half of the series. These findings further substantiate the implication of the amygdala in the pathogenesis of temporal lobe seizures with automatism and amnesia.

An apneic and tetraplegic infant with an open lumbosacral myelomeningocele and an Arnold-Chiari malformation is reviewed. An exuberant chronic aseptic meningitis with foreign body giant cells and immunoreactive keratin was present around the spinal cord and brainstem. This paper discusses the recognition and role of granulomatous meningitis in the clinical course and in the pathogenesis of the unusual cerebellar abnormalities found in this infant.

The extracellular environment of the neuron provides a heterogeneous milieu of survival and growth modulating molecular species subserving regulatory signals that operate in development, meditate activity-dependent enduring changes in synaptic connectivity, and promote or inhibit survival and axonal regeneration following insult. Parallel distributed processing networks in neurons, activated by these molecular species, can likely be recruited selectively to serve specific needs of the organism.

A stereotyped 32 Hz rolandic rhythm maximal over the mesial cortex and occurring only with voluntary movement is described in a patient with tonic postural seizures. This abnormal but nonictal rhythm, which is probably generated subcortically, is expressed synchronously at the level of the cortex and peripherally in the EMG.

3-Nitropropionic acid (3-NPA) — a suicide inhibitor of succinate dehydrogenase — is a widely distributed plant and fungal neurotoxin known to induce damage to basal ganglia, hippocampus, spinal tracts and peripheral nerves in animals. Recent reports from Northern China indicate that 3-NPA is also likely to be responsible for the development of putaminal necrosis with delayed dystonia in children after ingestion of mildewed sugar cane. This article discusses the role of 3-NPA in the causation of the disease in China, its neurotoxic effects in animals and the potential role for this compound as a probe of selective neuronal vulnerability.

Three fundamental types of cephalic axial skeletal-neural dysrapic disorders are analyzed, including: cranioschisis aperta with encephaloschisis (anencephaly and/or exencephaly), cranioschisis occulta with occipital encephalocele, and the Chiari malformation (occipital bone hypoplasia) with compression, deformation and displacement of hindbrain, cerebellum, and medulla. Both clinical and experimental (vitamin A induced) examples of these malformations are used. The study establishes that these are not simple neurological (neural tube defects) disorders as it has been generally assumed, but complex developmental malformations affecting primarily the formation of the axial basicranium (causing skeletal defects) and the elevation of the neural folds and neurocranium (causing neural defects), and, secondarily, the topography of the facial skeleton or viscerocranium (causing oropharyngeal defects). The pathology of these skeletal, neural, and oropharyngeal defects is analyzed, their embryonic origin explored, and their developmental interrelationships discussed. The study proposes that an early paraxial mesodermal insufficiency may be the original anomaly common to all the different malformations that constitutes this heterogeneous group of dysraphic disorders. At any time during the segmental formation of the embryonic skeletal-neural axis, a simple reduction in the number of paraxial mesodermal cells produced by the Hensen node/primitive streak complex, could impair the formation of the axial skeleton as well as the elevation of the neural folds thus interfering with their closure. The final type of malformation is determined by variations of the degree, time of occurrence, and duration of the paraxial mesodermal insufficiency.

Cerebral arteriovenous malformations (AVM), regardless of the mode of discovery, have an annual risk of hemorrhage of approximately 4 percent. A progressive obliterative vasculitis culminating in the occlusion of an AVM may be induced by the administration of radiation doses of approximately 20 Gy given in a single fraction. The process takes about two years and occlusion occurs in approximately 80% of patients so treated. Such a dose may be accurately administered to AVMs up to 3 cm in diameter with very little radiation imparted to the adjacent brain by means of multiple highly collimated radially arranged cobalt sources (the Gamma Knife) or by means of a modified linear accelerator turned through an arc or arcs with the target AVM as the centre of rotation. The Gamma Knife and the modified linear accelerator have nearly equal accuracy. Recent experience with modified linear accelerators indicates efficacy equal to the Gamma Knife. Both devices are effective treatment for small AVMs but the cost of modifying a pre-existing linear accelerator is only a few percent of the acquisition and installation costs of the Gamma Knife.

In a series of 23 patients, the commonest cause of accessory nerve palsy was surgical trauma at the time of lymph node biopsy. The less common causes were penetrating or blunt trauma and a few were of spontaneous onset. There was involvement of adjacent motor sensory nerves in about half of the patients. The prognosis was better following blunt trauma, stretch injuries and after a spontaneous onset. The anatomical relationships of the accessory nerve and aspects of the clinical picture and management are discussed.

Computed tomography and magnetic resonance imaging enable the identification of neuronal migration disorders during life. Several specific syndromes have been identified and early diagnosis of previously unrecognized entities is now possible. We report 51 patients with imaging. Thirty-two had a single widespread cortical dysplastic lesion. Twenty-eight had focal corticectomies. From a pathological standpoint, these encompassed focal cortical dysplasia (14 cases) and forme fruste of tuberous sclerosis (10 cases). These two groups of patients were indistinguishable from the clinical and radiological standpoint. In only two was the MRI examination normal. In addition, there were 10 with bilateral perisylvian dysplasia, four with diffuse cortical dysplasia or the "double cortex" syndrome, three with hemimegalencephaly, one with megalencephaly, and one with nodular neuronal heterotopia. The electroclinical and imaging findings led to the development of specific surgical strategies for the alleviation of the intractable seizures in each of these radiologically-defined syndromes.

Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age-related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest.effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function.

We compared the efficacy and tolerability of controlled-release carbamazepine (CBZ-CR) with conventional carbamazepine (CBZ) in 131 epileptic patients (both men and women, ages 6-65 years) in an open, multicentre, cross-over trial. Patients entered into the trial were previously on CBZ monotherapy or polytherapy. During the first 4 weeks, patients were treated with equivalent daily doses of CBZ and then switched to CBZ-CR for the subsequent 4 weeks. The majority of patients were switched to the more convenient b.i.d. dosing schedule of the controlled-release (CR) preparation without a detrimental effect on seizure frequency or adverse effects. In 44/131 (34%) of patients, the switch to CBZ-CR was accompanied by an improvement in tolerability, primarily due to a reduction in peak-dependent CNS side-effects such as tiredness, double or blurred vision, dizziness and ataxia. At the end of the study, investigators preferred CBZ-CR for 76% of their patients and 70% of the patients preferred CBZ-CR.