Cognitive-behavioral screening in elderly patients with new-onset epilepsy before treatment.

OBJECTIVES: Cognitive comorbidity at epilepsy onset reflects disease severity and provides a baseline estimate of reserve capacities with regard to the effects of epilepsy and its treatment. Given the high incidence of epilepsy at an older age, this study analyzed objective and subjective cognition as well as quality of life in elderly patients with new-onset focal epilepsy before initiation of anti-epileptic treatment. MATERIALS AND METHODS: A total of 257 untreated patients (60-95 years of age) with new-onset epilepsy underwent objective assessment of executive function (EpiTrack) and performed subjective ratings of cognition (Portland Neurotoxicity Scale) and quality of life (QoL; QOLIE-31). RESULTS: According to age-corrected norms, 58% of patients (N=257) demonstrated deficits in executive function; major determinants were cerebrovascular etiology, neurological comorbidity, and higher body mass index. Subjective ratings indicated deficits in up to 27% of patients. Self-perceived deficits were associated with neurological, cardiovascular, and/or psychiatric comorbidity, whereas poorer QoL was related to neurological comorbidity and female gender. Objectively assessed executive functions correlated with subjective social functioning, energy, motor function, and vigilance. CONCLUSIONS: We found a relatively high QoL, a low rate of subjective impairment, but a high incidence of objective executive deficits in untreated elderly patients with new-onset epilepsy. Neurological status and body mass index, rather than seizure frequency or severity, were risk factors for cognitive impairment. Given the relevance of cognition in the course of epilepsy and its treatment, routine screening before treatment initiation is highly recommended.

[Epilepsy in the elderly]. / Epilepsie im Alter.

Epilepsies frequently only start in old age and given the current demographic trend the prevalence of epilepsy in the elderly population will increase. This article summarizes the most relevant aspects of diagnosis and therapy in elderly patients with epilepsy. Guidelines, systematic reviews or meta-analyses are lacking and there are only three randomized controlled trials of epilepsy in the elderly. Clinically, seizures in the elderly may be missed since warning signs (auras) and seizure evolution into generalized tonic-clonic seizures are rarer in older people. Sudden loss of consciousness occurs more frequently with increasing age and poses a challenge for the differential diagnosis. Therapy is more complex due to frequent comorbidity and multiple drug therapy necessitating a cautious approach. Therapy is hampered by side effects and drug interactions making a definite diagnosis indispensable and requiring the use of newer generation antiepileptic drugs. In case of doubt, to ensure a safe diagnosis long-term video EEG should be considered even in the elderly before hazarding the negative consequences of a misdiagnosis for years.

[Epileptic seizures in the elderly]. / Epileptische Anfälle im Alter.

Given current demographic trends, the prevalence of epilepsy in the elderly population will increase. This review summarizes the most relevant clinical and therapeutic findings in elderly patients with epilepsy. Guidelines, systematic reviews, and meta-analysis are lacking, and there are only three randomized controlled trials of epilepsy in the elderly. Clinically, seizures in the elderly may be overlooked since warning signs (auras) and seizure evolution into generalized tonic-clonic seizures are rarer in old people. Sudden loss of consciousness occurs more frequently with increasing age, challenging differential diagnosis. Therapy is more complex due to frequent comorbidities and multiple drug therapies, requiring a cautious approach. Especially drug interactions need to be considered. Epileptic seizures seem to be better controlled by drugs in the elderly than in young people. Therapy is hampered by side effects and drug interactions, making definite diagnosis indispensable and bringing on the need for newer-generation antiepileptic drugs.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

Organization of cortical activities related to movement in humans.

The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.

Analysis and correction of ballistocardiogram contamination of EEG recordings in MR.

PURPOSE: To examine the influence of cardiac activity-related head movements and varying blood pulse frequencies on the shape of electroencephalography (EEG) recordings in a high magnetic field, and to implement a post-processing technique to eliminate cardiac activity-related artifacts. MATERIAL AND METHODS: Respiratory thoracic movements, changes of blood pulse frequency and passive head movements of 20 healthy subjects were examined outside and inside an MR magnet at rest in a simultaneously recorded 21-channel surface EEG. An electrocardiogram (ECG) was recorded simultaneously. On the basis of the correlation of the left ventricular ejection time (LVET) with the heart-rate, a post-processing heart-rate dependent subtraction of the cardiac activity-related artifacts of the EEG was developed. The quality of the post-processed EEG was tested by detecting alpha-activity in the pre- and post-processed EEGs. RESULTS: Inside the magnet, passive head motion but not respiratory thoracic movements resulted in EEG artifacts that correlated strongly with cardiac activity-related artifacts of the EEG. The blood pulse frequency influenced the appearance of the cardiac activity-related artifacts of the EEG. The removal of the cardiac activity-related artifacts of the EEG by the implemented post-processing algorithm resulted in an EEG of diagnostic quality with detected alpha-activity. CONCLUSION: When recording an EEG in MR environment, heart rate-dependent subtraction of EEG artifacts caused by ballistocardiogram contamination is essential to obtain EEG recordings of diagnostic quality and reliability.

Effects of the serotonin1B/1D receptor agonist zolmitriptan on motor cortical excitability in humans.

Oral administration of zolmitriptan, a novel 5-hydroxytriptamine receptor agonist, to eight healthy volunteers significantly reduced motor cortical excitability as tested by paired transcranial magnetic stimulation (TMS) at short interstimulus intervals. Zolmitriptan did not change motor thresholds to TMS or electromyographic silent period durations. We conclude that zolmitriptan acts centrally by reducing the inhibition within the motor cortex. The results suggest that the action of zolmitriptan on motor cortical excitability does not result from changes at the level of the cell membrane but from the influence on GABAergic inhibitory interneurons.

Transcranial magnetic stimulation for the treatment of seizures: a controlled study.

OBJECTIVE: To perform a controlled trial of transcranial magnetic stimulation (TMS). METHODS: Twenty-four patients with localization-related epilepsy were randomized to blinded active or placebo stimulation. Weekly seizure frequency was compared for 8 weeks before and after 1 week of 1-Hz TMS for 15 minutes twice daily. RESULTS: When the 8-week baseline and post-stimulation periods were compared, active patients had a mean seizure frequency reduction of 0.045 +/- 0.13 and sham-stimulated control subjects -0.004 +/- 0.20. Over 2 weeks, actively treated patients had a mean reduction in weekly seizure frequency of 0.16 +/- 0.18 and sham-stimulated control subjects 0.01 +/- 0.24. Neither difference was significant. CONCLUSION: The effect of TMS on seizure frequency was mild and short lived.

Motor cortex excitability in patients with focal epilepsy.

We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal (n = 7), extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the 'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the 'normal' hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.

Ictal SPECT hyperperfusion reflects the activation of the symptomatogenic cortex in spontaneous and electrically-induced non-habitual focal epileptic seizures: correlation with subdural EEG recordings.

We report a patient with left temporal lobe epilepsy and a left parietal angioma, in whom ictal SPECT showed hyperperfusion in a spontaneous and an electrically-induced, non-habitual focal seizure. A SPECT investigation during an habitual seizure originating in the left temporal lobe showed a left temporal hyperperfusion. Electrical stimulation of the parietal cortex adjacent to the location of a previously resected angioma using subdural electrodes resulted in a non-habitual seizure beginning with a unilateral somatosensory aura. Ictal SPECT of this seizure demonstrated contralateral central hyperperfusion. We conclude from our findings that ictal SPECT hyperperfusion reflects the activation of symptomatogenic cortex, which can be induced by both epileptic discharge and electrical stimulation.

[Costs of drug treatment of neurologic diseases: Parkinson disease, dystonia, epilepsy]. / Kosten der medikamentösen Behandlung neurologischer Erkrankungen: Morbus Parkinson, Dystonie, Epilepsie.

AIM: The costs of drug treatment were evaluated for Parkinson's disease, focal dystonias and epilepsy. METHODS: Retrospective analysis over a period of 12 months of 785 patients who visited regularly a neurological out-patient department. RESULTS: Drug treatment caused a mean annual expenditure of DM 3,920.- (US-($) 2590, pounds 1690) for Parkinson's disease (n = 409), DM 3,620.- (US-($) 2390; pounds 1550) for focal dystonias (n = 140) and DM 660.- (US-($) 435, pounds 280) for hemifacial spasm (n = 35) per patient.- In Parkinson's disease costs are dependent on the extent of the disease, the type involved and the presence or absence of motor fluctuations. In Hoehn and Yahr stage I we calculated costs of DM 2,230.- (US-($) 1470; pounds 960), in contrast to DM 11,870.- (US-($) 7830; pounds 5100) in Hoehn and Yahr stage V. The occurrence of fluctuations in motor ability increased annual costs to DM 6,010.- (US-($) 3970, pounds 2580); patients' treatment without motor fluctuations was cheaper (DM 2,700.-; US-($) 1780, pounds 1160).- The annual treatment costs of focal dystonias and facial hemispasm varied due to the location of the involuntary movement and the extent of symptoms: DM 4,900.- (US-($) 3300; pounds 2100) were calculated for the treatment of cervical dystonias, DM 1,480.- (US-($) 930; pounds 600) for the treatment of blepharo-spasm (oromandibular dystonia: DM 1,710.-; US-($) 1200; pounds 800) and DM 600.- (US-($) 470; pounds 300) for the treatment of facial hemispasm.- The drug treatment of epilepsy caused mean costs of DM 1,740.- (US-($) 1160; pounds 750) per year. There were marked differences concerning the different epileptic syndromes and types of seizure. CONCLUSION: Costs of drug treatment varied considerably in the three diseases depending on the course, the type and the different forms of the respective disease.

[Suggestion for a new, patient-oriented epilepsy classification]. / Vorschlag für eine neue patientenorientierte Epilepsieklassifikation.

The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

[Neurolisteriosis with acute myelitis]. / Akute Myelitis bei Neurolisteriose.

Listeriosis is a bacterial infection with Listeria monocytogenes mostly affecting immunocompromised patients. In every fourth case, the CNS is involved, usually as meningoencephalitis. This case report of an immunocompetent woman represents the first one of neurolisteriosis initially presenting as cervical myelitis and progressing to supratentorial areas of the brain. Diagnosis was based on universal polymerase chain reaction from a cortical brain biopsy, followed by sequencing of the amplified rDNA gene. Under antibiotic treatment with gentamycin and ampicillin, the patient slowly recovered and has been improving ever since.

The silent period induced by transcranial magnetic stimulation in muscles supplied by cranial nerves: normal data and changes in patients.

The silent period induced by transcranial magnetic stimulation of the sensorimotor cortex (Magstim 200, figure of eight coil, loop diameter 7 cm) in active muscles supplied by cranial nerves (mentalis, sternocleidomastoid, and genioglossus) was studied in 14 control subjects and nine patients with localised lesions of the sensorimotor cortex. In the patients, measurements of the silent period were also made in the first dorsal interosseus and tibialis anterior muscles. In the controls, there was a silent period in contralateral as well as ipsilateral cranial muscle and the duration of the silent period increased with increasing stimulus intensities. The mean duration of the silent period was around 140 ms in contralateral mentalis muscle and around 90 ms in contralateral sternocleidomastoid muscle at 1.2 x threshold stimulation strengths. Whereas the duration of the silent period in ipsilateral mentalis muscle was shorter than on the contralateral side it was similar on both sides in sternocleidomastoid muscle. In patients with focal lesions of the face associated primary motor cortex and corresponding central facial paresis, the silent period in mentalis muscle was shortened whereas it was unchanged or prolonged in limb muscles (first dorsal interosseus, tibialis anterior) with stimulation over the affected hemisphere. By contrast, in a patient with a lesion within the parietal cortex, the silent period in mentalis muscle was prolonged with stimulation of the affected side.

Functional organisation of corticonuclear pathways to motoneurones of lower facial muscles in man.

EMG responses were recorded from lower facial muscles (depressor labii inferioris or depressor anguli oris) of 12 normal subjects after magnetic stimulation of the motor cortex. Using a figure-of-eight stimulating coil, the largest responses were obtained from points around 8-10 cm lateral to the vertex. Usually they were bilateral and had the same latency (11-12 ms) on both sides of the face. Patients with complete Bell's palsy had no response in muscles on the same side as the lesion, indicating that the ipsilateral component to cortical stimulation was not the result of recrossing in the periphery of nerve fibres from the contralateral side. Single-unit studies showed that cortical stimulation produced two phases of motoneuronal facilitation: a short-latency (central motor delay from contralateral cortex to the intracranial portion of the facial nerve, 7.6 ms), short-duration (1- to 2-ms duration peak in the post-stimulus time histogram) input, which was more commonly evoked by contralateral than ipsilateral stimulation; and a longer latency (central delay > 15 ms), long-duration input evoked equally well from either hemisphere. The former may represent activity in a predominantly contralateral oligosynaptic corticobulbar pathway; the latter, a polysynaptic indirect (e.g. cortico-tegmento-nuclear) bilateral pathway to lower facial muscles.

Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease.

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.

Abnormalities of the balance between inhibition and excitation in the motor cortex of patients with cortical myoclonus.

Patients with cortical myoclonus may have purely focal or multifocal jerks, or they may have additional bilateral or generalized jerks, suggesting the spread of excitatory myoclonic activity between the cerebral hemispheres and across the sensorimotor cortex. The factors contributing to this spread of activity were investigated in 10 patients with multifocal cortical myoclonus and eight patients with multifocal and bilateral or generalized cortical myoclonus. The two groups were termed 'non- spreaders' and 'spreaders' respectively. Eight of the patients were also epileptic. Motor thresholds to single transcranial magnetic shocks at rest were higher in 'non- spreaders' (median 88%, range 45-100% of stimulator output) than either 'spreaders' (50%, range 26-90%, P=0.023) or health controls (38%, range 28-53%, P<0.001). This pathological elevation in motor threshold was not simply an effect of treatment with antiepileptic drugs. Paired transcranial magnetic stimuli were used to investigate ipsilateral cortico-cortical and transcallosal inhibition, There was less (MANOVA, P<0.05) ipsilateral inhibition at interstimulus intervals (ISIs) of 1-6 ms in 'spreaders' (mean 107+/-SEM 23% of control) compared with 'non- spreaders' (75+/-15%) or healthy subjects (59+/-10%). There was also less (P<0.05) transcallosal inhibition across inhibitory timings (10, 12 and 14 ms) in the 'spreaders' (98+/-6% of control) compared with the 'non-spreaders' (64+/-8%) or healthy subjects (59+/-6%). There was no relationship between ipsilateral cortico-cortical and transcallosal inhibition and the presence or absence of epilepsy, although non-epileptic patients did have higher motor thresholds (median 85%, range 32-100% of stimulator output) than either epileptic patients (50%, range 26-90%, P<0.001) or healthy controls (38%, range 28-53%, P=0.002). Abnormalities in ipsilateral and transcallosal inhibition appear to facilitate the spread of the cortical myoclonic activity responsible for bilateral and generalized jerks. However, these abnormalities in inhibition do not play a major role in the development of generalized seizures in patients with cortical myoclonus.

Effect of transcranial magnetic stimulation over the cerebellum on the excitability of human motor cortex.

There have been conflicting reports over whether it is possible to stimulate the human cerebellum through the intact scalp using transcranial magnetic stimulation. Here we attempt to clarify the situation in normal subjects by comparing the various methods which have been used. EMG responses evoked by magnetic stimulation over the motor cortex could be suppressed by a prior magnetic stimulus over the cerebellum but the onset latency of the effect varied according to the type of magnetic coil used. Inhibition began at a latency which ranged from 5 to 9 msec in different subjects if conditioning stimuli were given through a flat figure-of-eight coil held horizontally over the basal occiput. The effect lasted a further 6-10 msec. With a larger double cone coil, held vertically over the basal occiput, inhibition began earlier and at a more constant latency of 5 msec. It lasted only 3 msec. Stimulation of the C6/7 nerve roots in the brachial plexus with either an electrical or magnetic stimulus also could suppress EMG responses evoked by cortical stimulation. This began at a conditioning-test interval of 7 or 8 msec and lasted for some 5 msec. We suggest that two types of motor cortical suppression may be elicited from stimulation over the posterior neck/skull: a cerebellar effect starting at 5 msec, and a peripheral nerve effect starting later at 7/8 msec. Stimulation with a horizontal large figure-of-eight coil may produce a mixture of effects because the lower wing of the coil overlaps the posterior neck and can activate peripheral nerve fibres in the brachial plexus.

Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training.

Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter mediating alpha(1)-adrenergic function) and downregulated by alpha(1)-adrenergic antagonists. In spite of this, alpha(1)-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings. The purpose of this study was to determine the effects of a single oral dose of the alpha(1)-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent plasticity relative to a drug-free condition. These data suggest caution when using alpha(1)-adrenergic blockers in rehabilitative clinical settings following brain lesions.