In the first part of the paper supplementary information on Flechsig’s personality and his attitude to work is given which had not been sufficiently appreciated in English biographical notices. This is followed by translated excerpts from “Gehirn and Seele”, published in 1896, in which Flechsig introduced his myelogenetic localization of the cerebral cortex.

The second part is mainly a review of recent advances in neuroanatomical and neurophysiological research within those cortical regions in which Flechsig had been interested. A comparison between recent advances and Flechsig’s work demonstrates that Flechsig had definitive ideas on the solution of some of the outstanding problems but had been unable to resolve these with the techniques available at his time.

In 1896 Flechsig was still under the influence of Hermann Munk (1890) who had assumed that the cortex consisted of sensory centers, each equipped with efferent descending projection systems — olfactory, visual, auditory and — anterior to the last, the somatic sensory sphere (“Körperfühls-phäre”). This sphere also contained the kinaesthetic images of motor action induced by efferent fibers in the subcortical ganglia which, from Burdach (1819-26) until the time of Meynert, had been widely regarded as the highest motor centers. In 1905a, however, Flechsig had shed most of the influence of Munk. By then he had taken cognizance of the research of Grunbaum and Sherrington (1902, 1903) and realized that “in the highest anthropoid all stimulable points of the type of Fritsch and Hitzig are concentrated within one gyrus, namely the precentral gyrus, so that we can call this the motor gyrus … in man, too, the motor centers of the type of Fritsch and Hitzig are restricted to the precentral gyrus and the immediately adjacent part of the first frontal convolution. The central sulcus here too is the posterior boundary of the motor zone … Occasionally a larger or smaller part of the motor centers, especially of the fingers, gets into the postcentral convolution, but, according to my own embryological studies, only exceptionally. As a rule we have to assume that all voluntary motor impulses leave the cortex from the precentrai gyrus …”

Only recently has man begun to regard himself as mundane and not divine. This conceptual liberation has allowed him to ask frank questions concerning the physical and chemical mechanisms which determine or affect his behavior. Unfortunately the answers to these questions have been slow in coming. The reasons for this are two-fold: Basic ethical considerations preclude the experiments necessary to investigate the neural substrates of human behavior in man. Further, man’s behavior and nervous system are both so enormously complex and subtle, it is therefore unlikely that much real fundamental knowledge could be gained from such experiments if performed. It is more expedient to study simple behavior in simpler organisms than man to understand how nervous systems operate in general and, it is hoped, to eventually gain a better understanding of the human in particular. This tactic is known as the “model systems” approach. By discovering the strategies adopted by less complex nervous systems to deal with simple situations one can devise a realistic model of the neural mechanisms that control more complex behavior in more advanced animals.

Many animals have served as valuable sources of model systems. Among them the marine gastropod mollusc Aplysia has received considerable attention. In comparison to the human nervous system with approximately 50 billion neurons, the Aplysia nervous system contains relatively few neurons — about 20,000. Furthermore the study of the Aplysia nervous system has several other advantageous characteristics. A number of forms of behavioral plasticity that are found in all higher metazoans including man are also found in the Aplysia. These simple but non-trivial types of behavioral plasticity include habituation, sensitization and associative learning as well as easily defined qualities of neural function which we choose to call “behavioral states”. In addition the nervous system is composed of neurons which are large and, in many cases, easily identified by anatomical and physiological criteria so that the “same” cell can be studied in more than one animal under more than one set of experimental conditions. The cell bodies of the neurons in Aplysia, from which electrical recordings can be fairly easily obtained, are electrically close to their dendrites so that changes in postsynaptic potentials occurring during modifications of behavior can be monitored.

Seventy-five patients were treated between March 1976 and June 1980 for classical idiopathic tic douloureux. Fifty-five patients underwent percutaneous trigeminal rhizotomy (PTR) and twenty-four had posterior fossa microvascular decompression (M VD) of the trigeminal nerve. Four patients had both procedures. In the PTR group. 4% were immediate failures, 42% had a delayed recurrence of pain, while 54% remained totally pain free with an average follow-up of 30 months. In the MVD group, 12% were immediate failures, 17% had a delayed recurrence of pain, and 71% have remained free of pain with an average follow-up of 28 months. Neither procedure can be regarded as ideal surgical treatment for patients with pain refractory to medical treatment. Percutaneous rhizotomy has an established place because of its safety, particularly in elderly patients. A high rate of recurrent pain is to be expected. Microvascular decompression has appeal in younger patients because of its non-destructive nature but the long term efficacy of the procedure is not known.

An experimental model for the study of porphyric neuropathy is presented. Injection of either tetraphenylporphinesulfonate (TPPS), hematoporphyrin derivative (HpD), or delta-aminolevulinic acid (ALA) into mice resulted in markedly decreased motor nerve conduction velocity (MNCV). The MNCV returned to normal within one week following the injection of large doses of A LA, and within three weeks following the injection of close to lethal doses of HpD. hut there was no recovery of nerve function within 60 days following injection of substantially smaller doses of TPPS. Ultrastructural examination of motor nerves at various times following TPPS injection revealed the gradual development of structural abnormalities. Ultrastructional examination of the same nerves after a single dose of either A LA or Hp D failed to demonstrate any abnormalities.

The present observations call for precaution as to the use of TPPS as photosensitizer in human cancer treatment.

Eight patients with a histologically proven angiographically occult arteriovenous malformation of the brain had plain and infused computed tomographic (CT) examinations. In five cases angiography revealed a hypovascular mass and in three cases the angiogram was normal. On CT examination a high density lesion (six cases) and ventricular asymmetry (five cases) were demonstrated. In three patients presenting with intracerebral hemorrhage, the high density appearance and ventricular compression were accounted for by the presence of hematoma. In three of five seizure patients the high density lesion was associated with calcification while ipsilateral (one case) and contralateral (one case) enlargement of the lateral ventricle was seen. In five of the eight cases the vascular nature of the lesion was suggested by vascular enhancement of the infused CT scan. Glioma was a common misdiagnosis.

Extraneural spread of a cerebral glioma has been described infrequently. The present case provides an example of this unique mode of metastasis.

We report a case of acute neuropathy in a 46 year old female with porphyria variegata. Histologic, electron microscopic, and quantitative examinations of peripheral nerves were performed at onset of the neuropathy and at autopsy. The results revealed severe qualitative and quantitative changes in myelinated and unmyelinated fibers showing features indicative of an axonopathy with a distribution in keeping with a dying-back phenomenon.

Multimodality evoked potentials testing including PVEPs, SEPsand BAEPs was done in 112 patients who were known or suspected to have multiple sclerosis. The incidence of abnormal evoked potential findings in each of these systems was considered in patients in the different diagnostic categories of M.S. Results were also evaluated with respect to the presence of abnormal clinical visual, somatosensory, or brainstem signs. The PVEP was found to be the most frequently abnormal even in patients without clinical involvement in the visual system (45% of patients with definite, probable, or possible M.S.), the SEP was less frequently abnormal in the absence of clinical signs (35% in patients with M.S.), and the BA EP showed the lowest frequency of abnormalities in patients without brainstem signs (14% in patients with M.S.). Combining the three types of evoked potentials significantly increased the percentage of M. S. patients having abnormal findings, compared to any of these tests alone, with 97% of “definite” M.S. patients, 86% of “probable” M.S. patients and 63% of “possible” M. S. patients having at least one of these EP tests abnormal.

Our previous studies of cerebrovascular permeability in angiotensin-induced acute hypertension demonstrated that the principal mechanism resulting in increased permeability is enhanced pinositose. In order to exclude the possibility that the enhanced pinositose was a direct effect of exogenous angiotensin, cerebrovascular permeability alterations were studied in nonpharmacologically induced acute hypertension.

Rats receiving horseradish peroxidase (HRP) intravenously, were sacrificed 2½ minutes after the onset of hypertension induced by placing a clip on the abdominal aorta. These animals showed the same pattern of permeability alterations as had been observed previously in animals with angiotensin-induced acute hypertension. Focal segments of penetrating arterioles in the temporal and parietal cortex showed increased permeability to HRP. Permeable vessels showed increased numbers of pinocytotic vesicles and the interendothelial junctions revealed no alterations. Enhanced pinocytosis appears to be the principal mechanism resulting in increased cerebrovascular permeability in this model as well suggesting that the alterations of cerebrovascular permeability observed previously in angio-tensin-induced acute hypertension occur due to the hypertensive state and are not a direct drug effect of exogenous angiotensin.

Somatosensory evoked potentials (SEPs) were recorded following trigeminal nerve stimulation in 25 normal subjects. Mucosal stimulation of the lip resulted in a reduced stimulus artefact. The three initial peaks, N13, P19, and N30, measured respectively 12.8 ± 0.9 S−3, 19.3 ± 1.4 S−3 and 28.6 ± 1.7 S−3. Blink reflex studies were also performed in most of these subjects. In 41.4% of 29 patients with established or suspected multiple sclerosis, the trigeminal SEP was abnormal. Additional use of the blink reflex raised the overall incidence of trigeminal nerve dysfunction to 51.7%. None of the patients had clinical evidence of fifth nerve involvement either historically or on examination. Four of seven patients with progressive spinal MS and two patients whose only deficit was that of optic neuritis, had abnormal trigeminal SEPs. It is concluded that occult involvement of the pontine fifth nerve structures occurs frequently in MS despite the rarity of corresponding clinical findings. The trigeminal SEP is a useful additional neurophysiological method.

The eye movements of a patient with a left lateral medullary infarct (Wallenberg’s syndrome) were recorded using the scleral search coil in magnetic field technique. When asked to look at spontaneously appearing targets, saccades to the left were generally accurate hut those to the right reached the target by multiple step refixation saccades. Large amplitude rightward saccades were possible between two continuously visible targets or when making voluntary saccades in the dark.

Vertical saccades, up or down, between spontaneously appearing targets were always associated with a leftward eye movement (lateropulsion). Voluntary vertical saccades between continuously visible targets showed that upward movements had left lateropulsion but downward movements were normal. Vertical voluntary saccades in the dark were oblique, upward saccades showing left lateropulsion and downward saccades showing rightward deviation. The aberrant horizontal components of vertical saccades had amplitude and velocity characteristics for components of normal oblique saccades. Possibly impaired assessment of vertically with incorrect eye position information produced by the infarct accounts for the lateropulsion of saccades in Wallenberg’s syndrome.

We made an electroretinographic (ERG) and visual evoked potential (VEP) study of 12 patients with Friedreich’s ataxia whose diagnosis was established using the Quebec diagnostic criteria. ERGs and VEPs were elicited to the same stimulating conditions. Flash evoked luminance changes and pattern-specific evoked potentials to check and diamond stimuli were used. Statistical analysis of the data was made using independent sample t-tests. Significant VEP delays were present under all test conditions. The presence of significant interocular and interhemispheric delays as well as evidence of abnormal temporal dispersion of the VEP response suggest there to be both diffuse anterior visual system disease and retrochiasmal involvement in Friedreich’s ataxia. The implicit times of the ERG b-waves were statistically within normal limits but the waveforms were of low amplitude and deformed and there were significant interocular implicit time differences. These ERG results suggest there are retinal conduction abnormalities in Friedreich’s ataxia which possibly play a role in the genesis of the abnormal VEPs.

The computed tomographic (CT) examinations of one hundred and sixty patients with a clinical diagnosis of cerebral infarction were reviewed. A characteristic CT pattern was noted. Infused scans and follow-up studies allowed for considerable accuracy in diagnosis.

Fifty-five subjects undergoing carotid endarterectomy were grouped according to side of operation, i.e. right, left and bilateral. These subjects were administered a comprehensive neuropsychological battery prior to and six months following surgery. The performance of these subjects was compared with a control group undergoing surgical procedures that did not in volve the brain or cerebral vasculature, and a second control group composed of patients with cerebrovascular symptoms who were not operated. It was found that as a group the endarterectomy subjects improved on a greater percentage of measures. When various subgroups were examined, it was found that the right operated stroke patients improved on significantly more measures than any other group. The difference between right and left stroke patients was significant, but there was no difference between right and left TIA patients in the extent of improvement. These findings were discussed in terms of possible underlying mechanisms.

The authors report on a patient with a ruptured anterior communicating aneurysm treated surgically on the day following her subarachnoid hemorrhage (SAH). Repeated measurements of cerebral blood flow (rCBF) were carried out using the inhalational Xenon 133 method. Dramatic acute increases in rCBF occurred, coincident with clinical improvement, following mannitol, CSF drainage and dopamine. Later, further elevation to normal levels occurred following ventriculo-peritoneal shunting.

Some multiple sclerosis patients with 20/20 acuity complain of poor vision. In a previous report we accounted for this in our patient group by showing that multiple sclerosis had caused a depression of contrast sensitivity while sparing visual acuity. In this study we investigated whether some of this measured depression might be due to abnormally rapid or severe adaptation during the test procedure rather than a true permanent loss. Our finding was opposite to this supposition: adaptation was abnormally slight and/ or slow.

Depressed contrast sensitivity was not well correlated with abnormal adaptation to contrast. In patients whose contrast sensitivity losses were restricted to a band of spatial frequencies, we found no evidence that abnormalities of contrast adaptation were restricted to this same spatial frequency band. Further evidence of dissociation between abnormal contrast sensitivity and abnormal contrast adaptation is that some patients with normal contrast sensitivity showed abnormally small adaptation.

Our finding of abnormally slow or abnormally small contrast adaptation in MS patients seems to conflict with Enoch et al’s (1978) report of abnormally great adaptation after inspecting a bright stimulus. This apparent disagreement may be due to their use of prior dark adaptation, very bright adapting stimuli and patients in the acute stage of retrobulbar neuritis.