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Biomedical subjects

R Wennberg

Publications and source records attributed to R Wennberg.

At least 19 recordsLinked to original sources
PubMed2006

Movement disorders in patients taking anticonvulsants.

BACKGROUND: A wide variety of movement disorders may occur as a consequence of the administration of antiepileptic drugs (AEDs). Although it has been suggested that the risk of parkinsonism is 10-fold higher in those taking valproate as compared with other AEDs, there have been no large, systematic trials assessing this. AIM: To establish more precisely the prevalence of and risk factors for developing parkinsonism associated with valproate use,and to assess the occurrence of movement disorders with the newer AEDs. METHODS: Patients with epilepsy were recruited from the Toronto Western Hospital Epilepsy Clinic (University of Toronto, Toronto, Ontario, Canada). Each patient was examined by a movement disorder specialist who was blinded to the treatment status of the patient. RESULTS: 201 patients were included. Postural tremor was the most common movement disorder (45%), followed by parkinsonism (4.5%). The odds of having parkinsonism were 5 times higher with valproate than with other AEDs. No single factor predicted the presence of parkinsonism; however, many (5/9) of the patients concurrently used other drugs or had comorbidities that could have caused or exacerbated parkinsonism. None of the newer AEDs were clearly associated with the presence of movement disorders; however, the numbers were too small to make a formal analysis. CONCLUSION: Although the risk of parkinsonism with valproate is higher than with other AEDs, it is lower than originally reported. The cases available were not enough to accurately comment on the prevalence of movement disorders with the newer AEDs.

Adult↗
PubMed2006

The role of 1H magnetic resonance spectroscopy in pre-operative evaluation for epilepsy surgery. A meta-analysis.

PURPOSE: We aimed to assess the additional pre-operative value of (1)H MRS in identifying the epileptogenic zone (EZ) for epilepsy surgery by performing a meta-analysis considering publications from 1992 to 2003. METHODS: From an extensive computer and hand search 22 studies were included. For inclusion, studies had to report post-operative outcome and detailed diagnostic test results for each individual patient. Studies exclusively reporting on patients with brain tumors or on children were excluded. RESULTS: Great heterogeneity among studies regarding methodological and technical aspects and concerning evaluation and interpretation of data was observed. Only patients with intractable temporal lobe epilepsy were presented. Sixty-four percent of all patients and 72% of patients with good outcome had an ipsilateral MRS abnormality concordant with the EZ. The positive predictive value of all patients with ipsilateral MRS abnormality for good outcome was 82%. An odds ratio weighted by inverse variance showed a 4.891 better chance of seizure free outcome [CI=1.965-12.172; Q=2.748; d.f.=5; critical chi2-value=11.07] in patients with an ipsilateral MRS abnormality when compared to patients with bilateral MRS abnormalities. Data for MRI-negative patients were conflicting. One study stressed a role for MRS in patients with bilateral hippocampal atrophy at MRI. CONCLUSIONS: MRS still remains a research tool with clinical potential. Our findings indicate the connection of ipsilateral MRS abnormality to good outcome. The ability for prediction of post-operative outcome may depend on the assessed population. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation of these data.

Adolescent↗
PubMed2006

Bidirectional multisite seizure propagation in the intact isolated hippocampus: the multifocality of the seizure "focus".

Localizing the seizure focus is difficult and frequently, multiple sites are found. This reflects our poor understanding of the fundamental mechanisms of seizure generation and propagation. We used multisite electrophysiological recordings in two seizure models and voltage-sensitive dye imaging, to spatiotemporally characterize the initiation and propagation of seizures in an intact epileptogenic brain region, the isolated hippocampus. In low-magnesium perfusate, seizures always originated in the temporal region, and propagated along the septotemporal axis to the septal region. After the seizure spread across the hippocampus, the bursts within a seizure became bidirectional, with different propagation patterns at different frequencies. When the intact hippocampus was separated along the septotemporal axis, independent bidirectional activity was observed in the two halves, and region-specific cuts to the tissue reveal that the CA3 region is critical for seizure generation and propagation. In a second seizure model, using focal tetanic stimulation of the septal and temporal CA3 region, seizures always originated at the stimulated site with bidirectionality later developing at different frequencies, as noted in the low magnesium model, behavior compatible with coupled neuronal network oscillators. These data provide novel insights into the dynamic multifocality of seizure onset and propagation, revealing that the current concept of a single seizure "focus" is complex.

Animals↗
PubMed2005

EEG nonstationarity during intracranially recorded seizures: statistical and dynamical analysis.

OBJECTIVE: The investigation of nonstationarity in complex, multivariable signals, such as electroencephalographic (EEG) recordings, requires the application of different and novel approaches to analysis. In this study, we have divided the EEG recordings during epileptic seizures into sequential stages using spectral and statistical analysis, and have as well reconstructed discrete-time models (maps) that reflect dynamical (deterministic) properties of the EEG voltage time series. METHODS: Intracranial human EEG recordings with epileptic seizures from three different subjects with medically intractable temporal lobe epilepsy were studied. The methods of statistical (power spectra, wavelet spectra, and one-dimensional probability distribution functions) and dynamical (comparison of dynamical models) nonstationarity analysis were applied. RESULTS: Dynamical nonstationarity analysis revealed more detailed inner structure within the seizures than the statistical analysis. Three or four stages with different dynamics are typically present within seizures. The difference between interictal activity and seizure events was also more evident through dynamical analysis. CONCLUSIONS: Nonstationarity analysis can reveal temporal structure within an epileptic seizure, which could further understanding of how seizures evolve. The method could also be used for identification of seizure onset. SIGNIFICANCE: Our approach reveals new information about the temporal structure of seizures, which is inaccessible using conventional methods.

Electroencephalography↗
PubMed2004

Evolution of MRI changes and development of bilateral hippocampal sclerosis during long lasting generalised status epilepticus.

This report describes a previously healthy 28 year old patient with a 5 month period of intractable generalised status epilepticus (SE) of unknown aetiology with fatal outcome. Repeated magnetic resonance imaging (MRI) showed no pre-existing abnormality, but did show progressive cortical and hippocampal atrophy and T2 hyperintensity in both hippocampal formations, suggestive of progressive tissue damage. Post-mortem histopathological analysis revealed substantial neuronal cell loss including CA1 and CA4 sectors of the hippocampus compatible with bilateral hippocampal sclerosis. There was no evidence of systemic complications including arterial hypotension and hypoxia, hypoglycaemia, hyperpyrexia, or other confounding factors to account for these findings. This case provides further evidence of SE induced hippocampal damage in humans.

Adult↗
PubMed2003

Valproate induces reversible factor XIII deficiency with risk of perioperative bleeding.

The antiepileptic drug valproic acid (VPA) induces subclinical changes in both the intrinsic and extrinsic coagulation system. However, fatal bleeding is very rare. This study reports a 39-year-old patient who underwent selective amygdalohippocampectomy because of drug-resistant temporal lobe epilepsy. Preoperatively, the patient was on a combined therapy with VPA and topiramate, and routine coagulation laboratory parameters were entirely normal. Epilepsy surgery was immediately followed by severe intracranial bleeding events which promped repeated craniectomy. Extensive laboratory analyses revealed a factor XIII activity level of 17%, indicating factor XIII deficiency confirmed by a reduced XIIIA-antigen. After termination of treatment with VPA, factor XIII levels returned to normal. Control examinations after 9 and 24 months showed normal range values for all coagulation parameters, including factor XIII, platelet function, and von Willebrand factor. To our knowledge, this case is the first description of a well-documented, clinically relevant transient factor XIII-deficiency syndrome related to VPA treatment.

Adult↗
PubMed2003

Activation of electrocorticographic activity with remifentanil and alfentanil during neurosurgical excision of epileptogenic focus.

BACKGROUND: Opioids are known to stimulate surface electroencephalographic activity in patients with temporal lobe epilepsy. The objective of the current study was to compare the electrocorticographic activation effects of the newer short-acting opioid remifentanil with those of alfentanil during epilepsy surgery under general anaesthesia. METHODS: Thirteen patients undergoing temporal lobe epilepsy surgery under general anaesthesia received alfentanil 30 microg kg(-1) and remifentanil 1 microg kg(-1) as i.v. boluses in sequence. The design was a randomized double-blind cross-over study. After opening the dura, electrocorticogram (ECoG) electrode contact strips were placed over the temporal and supratemporal neocortex and depth electrodes were inserted in the amygdala and hippocampus. Alfentanil 30 microg kg(-1) or remifentanil 1 microg kg(-1) were administered randomly in a blinded fashion. The ECoG was recorded continuously before and after the injection of each drug. The interictal epileptiform activity (spikes and sharp waves) above baseline was analysed. RESULTS: Both drugs increased epileptiform activity especially that recorded from depth electrodes in the temporal limbic structures. No epileptiform activity was recorded from the electrodes overlying the supratemporal neocortex before or after drug administration. The more potent activator was alfentanil, which caused an increase in activation from baseline of 99.8% compared with 67.4% for remifentanil. In addition, alfentanil activated the epileptiform activity in 3 patients in which remifentanil had no effect. There were no changes in heart rate after the opioid boluses. Both remifentanil and alfentanil caused significant reductions in blood pressure at 3 and 5 min after administration. CONCLUSION: We conclude that at the doses used in this study, alfentanil is the better opioid for intraoperative activation of the ECoG in neurosurgical patients undergoing resection of a temporal lobe epileptic focus. This pharmacological activation of epileptiform activity assists in localizing and confirming the site of surgical excision. Neither alfentanil nor remifentanil activated epileptiform activity in non-epileptic brain tissue.

Adult↗
PubMed2001

Deep cerebral venous thrombosis: an illustrative case with reversible diencephalic dysfunction.

BACKGROUND: Isolated thrombosis of the deep cerebral veins is rare and its diagnosis can be difficult. Mortality is often high and little is known about the long-term prognosis. CASE REPORT: We report a 24-year-old woman with akinetic mutism and extensive bilateral thalamic lesions. CT and MRI allowed early diagnosis by demonstrating thrombosis within the internal cerebral veins, without the need for angiography. Heparin treatment was used safely despite the presence of thalamic and intraventricular hemorrhage. After five weeks, the patient recovered rapidly and remains well at 18 months. Serial MRI showed dramatic resolution of the imaging abnormalities. CONCLUSIONS: The clinical features and characteristic neuroimaging appearance of deep cerebral venous thrombosis should be recognized by physicians caring for stroke patients. Deep cerebral venous thrombosis can produce extensive venous congestion and vasogenic edema without early infarction. Excellent clinical recovery is possible even after severe and prolonged neurological deficits.

Adult↗
PubMed2000

Electroclinical analysis of postictal noserubbing.

BACKGROUND: Postictal noserubbing (PIN) has been identified as a good, albeit imperfect, lateralizing and localizing sign in human partial epilepsy, possibly related to ictal autonomic activation. METHODS: PIN was studied prospectively in a group of consecutive patients admitted for video-EEG monitoring, with the laterality of noserubbing correlated with electrographic sites of seizure onset, intra- and interhemispheric spread, and sites of seizure termination. RESULTS: PIN was significantly more frequent in temporal than extratemporal epilepsy (p<0.001; 23/41 (56%) patients and 41/197 (21%) seizures in temporal lobe epilepsy compared with 4/34 (12%) patients and 12/167 (7%) seizures in extratemporal epilepsy). The hand used to rub the nose was ipsilateral to the side of seizure onset in 83% of both temporal and extratemporal seizures. Seizures with contralateral PIN correlated with spread to the contralateral temporal lobe on scalp EEG (p<0.04). All extratemporal seizures with PIN showed spread to temporal lobe structures. One patient investigated with intracranial electrodes showed PIN only when ictal activity spread to involve the amygdala: seizures confined to the hippocampus were not associated with PIN. PIN was not observed in 63 nonepileptic events in 17 patients. Unexpectedly, one patient with primary generalized epilepsy showed typical PIN after 1/3 recorded absence seizures. CONCLUSIONS: This study confirms PIN as a good indicator of ipsilateral temporal lobe seizure onset. Instances of false lateralization and localization appear to reflect seizure spread to contralateral or ipsilateral temporal lobe structures, respectively. Involvement of the amygdala appears to be of prime importance for induction of PIN.

Amygdala↗
PubMed1999

Transient epileptic foci associated with intracranial hemorrhage in patients with subdural and epidural electrode placement.

We report two cases of transient epileptic foci in humans associated with placement of intracranial electrodes. The abnormalities consisted of restricted areas of active, almost continuous, rhythmic spiking, intermittently evolving into electrographic seizure activity, which resolved spontaneously within 3-4 days. The first occurred after placement of a subdural electrode grid and the second following insertion of epidural peg electrodes. Neuroimaging demonstrated a small subdural hematoma overlying the grid and a focal intraparenchymal hemorrhage underlying the affected epidural electrodes. The insertion of intracranial electrodes may be complicated by the induction of transient epileptic foci unrelated to a patient's typical epileptic generator.

Adult↗
PubMed1999

On the focal nature of inhibition and facilitation in the human motor cortex.

OBJECTIVE: To find the area of the human cortex from which inhibition and facilitation of corticospinal neurons could be obtained. METHODS: A patient with seizures had an array of 64 electrodes placed over the left fronto-temporal cortex. The motor evoked potential (MEP) elicited by stimulating through one pair of electrodes was conditioned by stimuli that were subthreshold for a MEP given through adjacent pairs of electrodes. RESULTS: The MEP recorded over the right abductor pollicis brevis produced by stimulating over the hand area of the left cortex could be inhibited (at intervals less than 5 ms) and facilitated (at intervals greater than 5 ms) by subthreshold conditioning stimuli delivered through neighbouring pairs of electrodes. The inhibition and facilitation were only obtained when the conditioning stimuli were delivered within 1-2 cm of the test site. The sites producing inhibition and facilitation were not identical. Conditioning stimuli over the face area did not inhibit the MEP produced by stimulating the hand area or vice versa. CONCLUSION: The inhibition and facilitation of corticospinal neurons projecting to a given muscle arise from small areas close to those corticospinal neurons.

Electric Stimulation↗
PubMed1999

Cortical reflex myoclonus studied with cortical electrodes.

OBJECTIVE: To study the mechanism of cortical reflex myoclonus. METHODS: A patient with stimulus sensitive myoclonus of the left foot had an array of subdural electrodes placed over the right sensorimotor cortex. RESULTS: Stimulation through one of the electrodes (contact 13) facilitated leg muscles with the shortest latency and was presumed to lie over the motor cortex. Tibial nerve stimulation evoked a potential with the shortest latency 1 cm further posteriorly (contacts 11-12). These contacts were presumed to lie over the sensory cortex. The potential at 11-12 was followed by a much larger potential that reversed polarity at contact 13. Back averaging from spontaneous myoclonic jerks showed a cortical premovement potential which reversed polarity at contact 13. The threshold for the motor evoked potential in leg muscles evoked by transcranial magnetic stimulation was lower on the affected side. Electrical stimulation through contact 13 produced cortical potentials that could be recorded at adjacent contacts. The combination of a positive potential followed by a negative potential recurred at approximately 35-40 ms intervals, each positive potential generating a myoclonic jerk. Additional waves resembling I waves accompanied only the first positive potential. Surgical removal of the cortex under electrode 13 abolished the myoclonus. CONCLUSIONS: The myoclonic jerks arose in the motor cortex. We postulate that there is increased excitability or synchronization of the cortical neurons at that site. The spontaneous, peripherally induced and recurrent cortical potentials and myoclonic jerks can occur without participation of the circuitry of the presumed I waves.

Aged↗
PubMed1999

Reversible paraneoplastic encephalomyelitis associated with a benign ovarian teratoma.

BACKGROUND: Paraneoplastic encephalomyelitis (PEM) is a well characterized, and typically irreversible, paraneoplastic syndrome, usually associated with small cell lung cancer or other malignancy. We describe a case of a young woman with a benign ovarian teratoma who presented with a reversible PEM. CASE REPORT: A 24-year-old woman presented with a three week history of memory impairment, unusual behavior, personality changes, auditory hallucinations, hypersomnolence and binocular biplopia. On admission she was disoriented and inattentive with impaired short term memory. Small doses of lorazepam (1 mg), given for episodic agitation, repeatedly induced multidirectional bilateral nystagmus and a skew deviation, but her neurological examination was otherwise normal. A left-sided pelvic mass was palpable. Brain MRI pre- and post-gadolinium was normal. There was a mild CSF pleocytosis and an EEG showed minimal bilateral background activity irregularities. There were no other laboratory abnormalities. Two weeks after admission, she clinically deteriorated developing central respiratory failure and a flaccid paraplegia. Repeat MRI showed an area of increased T2 weighted signal in the medulla and three similar areas in the spinal cord. Following removal of her tumor, treatment with high dose corticosteroids and intravenous immunoglobulin, she ultimately made a full recovery. Pathology revealed the tumor to be a benign ovarian cystic teratoma. CONCLUSIONS: This is the first report of a reversible PEM seen in association with a benign tumor, in this case a mature ovarian teratoma. Presumably, an immune response directed against neural clements of the teratoma cross-reacted with normal brain, brainstem and spinal cord antigens to cause neurologic symptoms. Tumor removal was followed by neurologic recovery.

Adult↗