Contralateral Spread Research Articles

Metabolic changes and electro-clinical patterns in mesio-temporal lobe epilepsy: a correlative study.

Interictal hypometabolism is commonly found in mesio-temporal lobe epilepsy (MTLE), but its pathophysiology remains incompletely understood. We hypothesized that metabolic changes reflect the preferential networks involved by ictal discharges. We analysed the topography of interictal hypometabolism according to electro-clinical patterns in 50 patients with unilateral hippocampal sclerosis (HS) and consistent features of MTLE. Based on electro-clinical correlations, we identified four groups: (i) mesial group (13 cases) characterized by mesial seizure onset without evidence of early spread beyond the temporal lobe; (ii) anterior mesio-lateral group (AML; 18 cases) with early anterior spread involving the anterior lateral temporal cortex and insulo-fronto-opercular areas; (iii) widespread mesio-lateral group (WML; 15 cases) with wide spread (involving both anterior and posterior lateral temporal and perisylvian areas); and (iv) bitemporal (BT) group (four cases) with early contralateral temporal spread. Results of [18F]fluorodeoxyglucose-PET imaging in each group were compared with those of 10 control subjects using statistical parametric mapping software (SPM99). MRI data and surgical outcome in each group were compared with metabolic findings. Hypometabolism was limited to hippocampal gyrus, temporal pole and insula in the mesial group. Gradual involvement of lateral temporal cortex, insula and perisylvian areas was observed in the AML and WML groups. The BT group differed from the others with mild bitemporal involvement, bilateral insular hypometabolism and longer epilepsy duration. MRI structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypometabolism. However, temporal hypometabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n = 43), seizure-free outcome was obtained in 82%. Surgical outcome appeared more favourable in the mesial group. However, the difference between the four groups was not significant. Our results suggest that hypometabolism in MTLE may be related to ictal discharge generation and spread pathways, even if structural changes and epilepsy duration may also play a role.

Selective neck dissection for no neck supraglottic carcinoma

The study comprised patients with a supraglottic laryngeal carcinoma treated in the period 1976–1993. All patients had primary surgery. They all had clinically negative findings in the neck (No). Bilateral selective neck dissection at the levels II–IV was performed in all patients.One hundred and ninety-three patients were studied. The occult cervical node metastases were found in 18% (35/193). The incidence of occult metastases of the epilarynx was 19% (14/72) and in the supraglottis excluding epilarynx was 17% (21/121). Ipsilateral occult metastases were more common 77% (27/35), but both bilateral and contralateral spread was also seen (14%, 5/35 and 9%, 3/35).Postoperative radiotherapy was given to all patients with verified occult metastases. Only in two (1%) did metastases develop subsequently, indicating the effectiveness of planned post-operative radiotherapy.

Early experience with continuous cervical paravertebral block using a stimulating catheter

Background and Objectives: This study reports our early experience with continuous cervical paravertebral block (CCPVB) using a stimulating catheter for the management of acute pain after shoulder surgery. Methods: This prospective observational study presents 256 CCPVB for pain relief after 14 different shoulder operations. Surgery was performed under general anesthesia and blocks were placed prior to induction of general anesthesia (n = 81 [32%]), after induction of general anesthesia (n = 116 [45%]), or postoperatively in the recovery room (n = 59 [23%]). A bolus dose of 30 mL of 0.5% ropivacaine was followed by an infusion of 0.1 mL/kg/h of 0.2% ropivacaine. Patient- or nurse-initiated bolus doses of 10 mL of the same drug were used for breakthrough pain and rescue analgesics were available. Postoperative pain, patient satisfaction, and motor function in different parts of the upper limb were evaluated immediately after surgery (time 0), and then 6, 12, 24, 48, 60 hours, and 14 days postoperatively. Results: An average of 2 (range 1–7) attempts were needed to advance the catheter while still stimulating the nerve. Average postoperative pain ranged from 0.27 ± 1.04 cm to 0.78 ± 1.56 cm (mean ± SD) on a visual analog scale (VAS) (0–10 cm) for the first 48 hours and 3.8 ± 2.1 cm and 3.5 ± 2.4 cm at 60 hours and 14 days, respectively. Patient satisfaction on a VAS of 0 to 5 was 4.19 ± 1.1, 4.28 ± 1.01, and 4.69 ± 1.05 at times 0, 6 hours, and 14 days, respectively. Motor function returned to normal in the fingers within 24 hours and in the shoulder within 60 hours. Complications included Horner’s syndrome (40%), dyspnea (8%), superficial skin infection (5%), posterior neck pain (22%), subclavian artery puncture (1%), contralateral epidural spread (4%), and 8% of the patients complained of an unpleasant “dead feeling” of the arm. Ninety-one percent of patients would request CCPVB again for future shoulder surgery. There was no evidence of nerve damage.

Molecular pathogenesis of bilateral breast cancer

Bilateral breast cancer (biBC) offers intriguing possibilities for molecular genetic investigations, however it is disproportionally less studied than its unilateral counterpart. By now, genetic research has succeeded to resolve at least two important aspects of biBC pathogenesis. First, it has been confirmed, that the vast majority if not all biBC arise due to clonally independent events but not due to contralateral metastatic spread. Second, unselected biBC cases have been shown to have a modest prevalence of BRCA germ-line mutations (approximately 5%), although a considerable frequency of BRCA defects (up to 20%) has been observed in early-onset and/or familial forms of the disease. Other data related to biBC appear to be at suggestive stage. Recent reports demonstrate, that the tumors forming biBC pair may show similarities of their molecular portraits, especially if they develop synchronously. This observations imply that the host factors may determine not only the level of breast cancer susceptibility, but also the molecular variant of the disease development. Apart from this, biBC may serve as a very demonstrative case group in the studies of breast cancer predisposing low-penetrance gene polymorphisms, because it is more likely to accumulate unfavorable allele combinations than the unilateral patients. The utility of this approach has been already exemplified by several scientific publications. Further research on the biBC molecular pathogenesis may significantly contribute to the general understanding of the process of malignant transformation.

Postictal language dysfunction in complex partial seizures: effect of contralateral ictal spread.

The authors report postictal language evaluation in patients monitored with bitemporal depth electrodes. Patients whose seizures began in the nondominant temporal lobe and propagated to the contralateral temporal lobe had a prolonged postictal language delay (PILD) with paraphasic errors compared with seizures that did not spread. Shorter propagation time was also associated with a longer PILD. Our study suggests that ictal involvement of the dominant temporal lobe is important in postictal language behavior.

Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer.

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source

Objective: To demonstrate an oncologic basis for the recommendation to perform bilateral tonsillectomy as a routine measure in the search for a primary mucosal lesion in patients presenting with cervical nodal metastasis of squamous cell carcinoma (SCC). Study design: A case series of individuals selected from a 3-year period is reported. Setting: Academic medical center. Results: Each individual presented with metastatic squamous cell carcinoma in a cervical lymph node from an unknown primary source. In each case, the primary source was identified in a tonsillectomy specimen, either located contralateral to the node, or in both tonsils. Conclusions: The rate of contralateral spread of metastatic cancer from occult tonsil lesions appears to approach 10%. For this reason, bilateral tonsillectomy is recommended as a routine step in the search for the occult primary in patients presenting with cervical metastasis of SCC and palatine tonsils intact. (Otolaryngol Head Neck Surg 2001;124:331-3.)

GABAA receptor antisense epilepsy: Histological changes following infusion of antisense oligodeoxynucleotide to GABAA receptor γ2 subunit into rat hippocampus

A deficiency of neuronal inhibition mediated by γ-aminobutyric acid (GABA) via the GABAA receptor complex has been hypothesised to be a central factor in epileptogenesis. Intrahippocampal infusion of antisense oligodeoxynucleotide (ODN) to the GABAA receptor γ2 subunit in rats leads to electrographic limbic status epilepticus. In this model, epileptic phenomena are accompanied by loss of hippocampal neurones. The purpose of the present study was to investigate the time-course of morphological changes following hippocampal antisense 'knockdown' of the GABAA receptor γ2 subunit. γ2 subunit antisense ODN was infused continuously into the right hippocampus for periods between 1 and 5 days. After about 4 days of infusion, pronounced neurodegenerative changes were consistently observed within the ipsilateral hippocampus. In general, marked loss of CA3 pyramidal cells was found. The notion that the histological changes induced by the antisense ODN were specific to the applied ODN sequence was supported by the finding that a mismatch control ODN did not induce neurodegenerative changes, except for a small lesion in the immediate vicinity of the infusion site. Extensive ipsilateral hippocampal infiltration with monocytes and macrophages was a feature of antisense ODN infusion, but was considerably less pronounced after the infusion of control ODN. Immunocytochemistry using an antibody labeling glial fibrillary acidic protein (GFAP), revealed marked astroglial hypertrophy/proliferation after 4 days of antisense treatment, i.e., coincident with the development of neurodegeneration, in the ipsilateral hippocampus. At this time GFAP-immunoreactivity was also evident in the contralateral hippocampus, indicating contralateral spread of seizure activity. [Neurol Res 2001; 23: 39-46]

Periodic lateralized epileptiform discharges: association with seizures

The clinical features and EEGs of 45 consecutive patients (40 adults and 5 children) who had periodic lateralized epileptiform discharges (PLEDs) were reviewed to determine the relationship between seizures and PLEDs. Focal encephalitis and ischemic stroke were the most frequent underlying processes for adult patients . All of the children, but only six of the adults, had long-lasting cerebral disorders whereas the remaining adults had acute or subacute illness. There were 38 patients (84.4%) experiencing a seizure disorder. Twenty-six of them had their first seizure during their acute illness, as the pattern of PLED was encountered. Eight cases had status epilepticus, and seven of them had epilepsia partialis continua. Nineteen patients had a recent seizure in the day when PLEDs were observed but not during EEG recording; 12 patients had their seizures within 10 days before the observation of PLED. PLEDs were grouped into three categories with respect to their extensions: lateralized to one hemisphere (n= 22), localized in one region (n= 17) and being prominent over one side with contralateral spread (n= 6). The last group was found to be more closely associated with frequent seizures or status epilepticus than the other two groups. Our results showed that PLEDs were highly correlated with recent seizures in the majority of the patients. These EEG findings may be considered as a manifestation of an increased neuronal excitability caused by different etiologies; but not an ictal pattern.

Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy.

To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.

Occult metastases from supraglottic laryngeal carcinoma.

One hundred and sixty-one patients with a supraglottic laryngeal carcinoma and clinically negative neck were studied. All patients had primary surgery and occult cervical node metastases were found in 18% (29/161). Local dissemination of tumour in the epilarynx did not influence the incidence of occult metastases, while the incidence of occult metastases increased with the degree of local spread in the supraglottis excluding the epilarynx. Ipsilateral occult metastases were more common (76%, 22/29), but both bilateral and contralateral spread was also seen (14%, 4/29 and 10%, 3/29, respectively).

Variation between centers in electrophysiologic techniques used in lumbosacral selective dorsal rhizotomy for spastic cerebral palsy.

The extent of variation between centers in the electrophysiologic techniques used in lumbosacral selective dorsal rhizotomy (SDR) for spastic cerebral palsy was studied using a questionnaire survey. Nineteen centers completed the questionnaire, and the responses were analyzed for those 16 centers in which the extent of dorsal root section was guided by intraoperative electrophysiologic responses. Consistent techniques included: use of unipolar stimulating electrodes (11 of 15 responses); stimulation < 4 cm from the root exit foramen (14 of 16); separation of dorsal roots into three to eight rootlets each (14 of 16); tetanic stimulation frequency of 50 Hz (11 of 16); tetanic stimulation at 100% of threshold (13 of 16); recording from multiple lower limb muscles simultaneously (16 of 16), and using contralateral spread of the response as a major criterion of electrophysiologic abnormality (13 of 16). There was more variation (< 11 of 16 concurrence) with respect to the use of a constant current versus constant voltage stimulator; the location of the cathode of the stimulating electrode relative to the anode; the definition of the threshold for a response; whether threshold was determined from stimulation of a dorsal root, or individual rootlets; the type of recording electrodes (needle versus surface), and the relative importance of electrophysiologic versus clinical findings in determining how much of each dorsal root to cut. In 10 centers, SDR would proceed without the benefit of electrophysiologic guidance if the equipment should fail intraoperatively (only if quadriplegic in 4), and this had happened in 6. The results indicate significant variation in many aspects of electrophysiologically guided SDR.

The validity of electrophysiological criteria used in selective functional posterior rhizotomy for treatment of spastic cerebral palsy.

Although selective functional posterior rhizotomy (SFPR) is an established procedure for the treatment of spasticity, the electrophysiological criteria used to define which posterior rootlets should be cut have not been standardized. The purpose of this study was to determine the validity of the intraoperative electrophysiological criteria used to select posterior rootlets for sectioning in SFPR. Intraoperative stimulation of posterior lumbosacral nerve roots and rootlets, using a 50-Hz stimulus at threshold intensity, was performed in five nonspastic children (controls) undergoing laminectomy for spinal cord untethering and in 32 spastic patients undergoing SFPR. Electromyographic responses were recorded in the upper and lower limbs, the neck, and the face. The pattern of sustained responses was assessed in detail in 17 additional patients who had previously undergone SFPR and in the five controls. Sustained responses with ipsilateral lower limb extrasegmental spread occurred in both spastic patients and the control group. Contralateral lower limb spread and suprasegmental spread to the upper limbs, neck, and face were found only in spastic children. Sustained responses with an incremental pattern were restricted to the spastic population and correlated well with the extent of contralateral and suprasegmental spread, whereas decremental patterns were not associated with contralateral spread. It is concluded that contralateral and suprasegmental spread into the upper limbs, neck, and face, and incremental responses are probably valid criteria of abnormality.

The human dorsal hippocampal commissure. An anatomically identifiable and functional pathway.

The hippocampal commissural system in the human brain was found to be similar to that of non-human primates. Three normal serially sectioned human brains were studied in coronal and sagittal sections. Morphological criteria that had been validated in experimental studies on the hippocampal commissures in monkeys (Amaral et al., 1984; Demeter et al., 1985; Lamantia and Rakic, 1990) were applied to the study of these human brains. It was found that while a further reduction in the ventral hippocampal commissure has taken place in human phylogeny leading to its near or total disappearance, the dorsal hippocampal commissure is well developed and represents a sizable fibre tract. It crosses the midline under the rostral portion of the splenium and the caudal part of the body of the corpus callosum. Its fibres as they travel between the splenium and the hippocampal formation attach themselves to the fornix and the inferior portion of the forceps major of the corpus callosum. In its morphology the human dorsal hippocampal commissure fully conforms to that reported in experimental tracer studies in the monkey (Amaral et al., 1984; Demeter et al., 1985). Depth electrode EEG recordings of temporal lobe seizures show, in some instances, a pattern of contralateral spread which strongly suggests that it occurred through the dorsal hippocampal commissure. This statement is based on a careful analysis of the different patterns of contralateral spread of seizure discharge in the light of the known anatomical connections of mesial temporal structures through both direct commissural pathways and through possible indirect ones involving subcortical structures or the frontal lobe. For seizure discharges originating in mesial temporal structures of one side with spread to the contralateral hippocampus before any involvement of the contralateral isocortex the dorsal hippocampal commissure is the only likely pathway of contralateral propagation. Alternative routes appear unlikely in the light of the known primate anatomy of the commissural and other connections of the temporal lobe. Thus humans, despite claims to the contrary (Wilson et al., 1987, 1990, 1991), seem to possess a functional dorsal hippocampal commissure. Some patterns of seizure spread observed in this study which seem to utilize the dorsal hippocampal commissure may be relevant for two phenomena that are of clinical interest: (i) pure amnestic seizures (Palmini et al., 1992); (ii) false lateralization of seizure onset in extracranial EEG recordings in the type III of contralateral seizure spread as defined in this study.

Observations on electrical stimulation of lumbosacral nerve roots in children with and without lower limb spasticity.

Selective functional posterior rhizotomy (SFPR) is a popular operation for the treatment of spasticity in children with cerebral palsy, but the physiologic basis of the procedure is poorly understood. As part of SFPR operations in 60 consecutive children, the responses to electrical stimulation of posterior lumbosacral roots and rootlets, and the corresponding anterior roots were studied. In addition, similar electrical stimulation of posterior roots was performed in four nonspastic "control" children. Sustained responses to 50 Hz stimulation, one of the criteria used to signify abnormality in the spastic children, was found frequently in the "control" children. Contralateral spread to the lower limb muscles and suprasegmental spread to the upper limbs, face, and neck were determined to be the most valid criteria which differentiated abnormal from normal responses. Stimulation of anterior nerve roots at 50 Hz caused sustained responses and ipsilateral lower limb spread, at a low threshold compared to that of corresponding posterior roots. The results of this study bring into question the validity of some of the criteria that are used to select abnormal posterior rootlets in the SFPR procedure, and suggest criteria that may be more valid based on findings in nonspastic children.

Double-lumen Endotracheal Tubes

Double-lumen endotracheal tubes have revolutionized the anesthetic management of patients undergoing thoracic surgery. As experience with the techniques of DLT placement and monitoring progress, an increasing number of uses in the intensive care unit will evolve. Benefit from differential lung ventilation in patients with respiratory failure from unilateral lung diseases and bronchopleural fistulae has been documented in selected instances. Isolation of the lungs to prevent contralateral spread of hemoptysis is occasionally of assistance. Frequent monitoring of DLT position while understanding the physiology of differential lung ventilation will minimize complications with these tubes.

Changes in seizure activity following anticonvulsant drug withdrawal

We retrospectively studied the effects of changing antiepileptic drug levels on patterns of seizure discharge in 8 patients investigated with intracerebral electrodes during presurgical evaluation. We compared seizures recorded at high levels of medication to seizures recorded at low levels for changes in seizure duration, duration from unilateral onset to contralateral spread, inter- and intrahemispheric coherence, and morphology of EEG discharges. Seizures were more frequent with low medication, as was secondary generalization. Reduction in medication did not affect the morphology of discharges at onset, duration to contralateral spread, and coherence between EEG discharges. Seizures of similar type (eg, complex partial seizures without secondary generalization) were not longer with low than with high medication. Whereas medication clearly affects seizure frequency and generalization, it has little effect on the pattern of early parts of seizures. In particular, we found no evidence that seizure discharges become bilateral or generalized more quickly when medication is reduced.

Inter-hemispheric propagation of human mesial temporal lobe seizures: a coherence/phase analysis

Intra- and inter-hemispheric propagation of ictal discharges was analyzed with computer techniques in 10 patients with complex partial seizures of mesial temporal lobe origin in whom depth electrodes had been stereotaxically implanted. Coherence and phase analysis of seizure discharges was used to detect the emergence of linear relationships between all possible pairs of surface and depth recording derivations both between and within hemispheres. This analysis included mesial temporal, lateral temporal, and frontal lobe sites during both the onset and inter-hemispheric propagation of 28 ictal episodes. Although strong intra-hemispheric coherences and linear phase spectra reliably emerged in both the epileptogenic and non-epileptogenic hemispheres during seizure onset and contralateral spread, these relationships were usually not observed for inter-hemispheric comparisons. Only 3 of 10 patients demonstrated some degree of consistency in the emergence of significant wideband coherences and linear phase spectra between left and right mesial temporal sites during the inter-hemispherics propagation of ictal discharges. Mesial temporal lobe sites which demonstrated such a relationship included the amygdala, pes hippocampi, and parahippocampal gyrus. In 7 of 10 patients, lateral temporal derivations were sampled during ictal events; the emergence of linear relationships between left and right lateral temporal derivations during inter-hemispheric propagation was observed for only two. Various frontal lobe sites were monitored in 3 of the 10 patients; the emergence of linear relationships was observed only between left and right orbitofrontal derivations in the one patient for whom this region was sampled. These results suggest that the hippocampal commissure, parts of the corpus callosum, and parts of the anterior commissure may be relatively unimportant for the inter-hemispheric propagation of mesial temporal seizures in man. Future studies in non-human primates may reveal that ictal discharges which originate in the mesial temporal region propagate preferentially via brain-stem pathways to contralateral homologous regions.

Interhemispheric interactions in seizures of focal onset: data from human intracranial recordings

Interactions between the two hemispheres were studied during seizures recorded in 8 epileptic patients having chronic intracranial electrodes. Seven had temporal lobe foci and one a frontal-central focus. Strength of interaction was measured by the coherence between the EEGs from symmetrical contralateral locations. Time delays of a few milliseconds between discharges were computed by the coherence and phase method. The evolution of interactions was followed from the time a seizure of focal onset had become bilateral to its end. It was found that interhemispheric coherence was generally low throughout seizures, highest value being reached early in the seizure at the time of spread, or at the very end. Time delays most often indicated a lead from the side of onset, whether they were measured early or late in the seizure. Exceptions to these results were found in 2 of 3 patients with bilateral independent onsets: interhemispheric coherence was higher and time leads were always from the same side, independently of the side of onset. If it is assumed that high interhemispheric coherence is mediated by direct connections such as corpus callosum and anterior commissure, then these results can be interpreted as follows: the major commissures do not play an important role in contralateral spread of temporal lobe seizures although they are sometimes active, particularly at initial spread and at seizure end. Time leads from the side of onset indicate that the focus retains an influence over the contralateral discharge throughout the seizure. A different situation may exist with independent bitemporal foci.

Cerebral glucose utilization: Local changes after microinoculation of scrapie agent in hamster

The effects of scrapie agent on local cerebral energy metabolism were studied by the [ 14C]2-deoxyglucose (2-DG) autoradiographic method of Sokoloff et al. after stereomicroinoculation (0.5 μl, 10 −2 of scrapie suspension) in hamster left striatum. From a group of 20 hamsters inoculated, 2 animals were killed every 10 days from the 30th day after inoculation to the terminal stage of the disease. Experiments were carried out according to the qualitative 2-DG procedure and cerebral autoradiographs of inoculated animals were compared to those of 3 controls. The results show changes of local cerebral glucose utilization in some discrete brain regions, ipsilateral to the side of inoculation, and their sequential spreading to other cerebral structures with a definite order: left anterior thalamus, left posterior thalamus, then medial geniculate body (ipsilateral, then controlateral), and finally some brainstem nuclei (inferior colliculus, superior olivary nuclues); the inoculated striatum is affected very late, after clinical signs. Metabolic changes which first occur ipsilaterally to the side of inoculation precede the clinical symptoms, while their contralateral spreading is concomitant with the clinical signs. The data demonstrate a rostral-caudal sequence of the cerebral metabolic changes, ipsilateral to the side of inoculation, which may reflect in part the slow spread of agent in the central nervous system from the inoculation site.