Fixation-off sensitivity.

Fixation-off sensitivity (FOS) is a phenomenon induced by elimination of central vision/fixation, and may either manifest clinically with seizures or only represent an EEG abnormality. FOS is characterized by posterior or generalized epileptiform discharges that consistently occur after closing of the eyes and last as long as the eyes are closed. It is most commonly encountered in patients with idiopathic childhood occipital epilepsies, but may also be observed in cases of symptomatic or cryptogenic focal and generalized epilepsies, as well as in asymptomatic non-epileptic individuals. FOS should be differentiated from pure forms of scotosensitivity, in which EEG discharges or epileptic seizures are elicited by darkness, and from epileptiform discharges triggered by eye closure, which refer to eye closure sensitivity. Although FOS is probably associated with occipital hyperexcitability its intrinsic epileptogenic potential is presumed to be low.

IV Valproate in generalized convulsive status epilepticus: a systematic review.

Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.

f-MRI in Epilepsy with Spike and Wave Activity Evoked by Eye Closure: Different Bold Activation in a Patient with Idiopathic Partial Epilepsy with Occipital Spikes and a Control Group.

We performed functional magnetic resonance imaging (fMRI) in a 30-year-old man with idiopathic partial epilepsy with occipital spikes whose scalp EEG activity was characterized by persistent epileptiform discharges on eye closure, ceasing upon eye opening. We compared BOLD activation in the patient and in a control group of three normal volunteers. f-MRI showed that occipital cortex and frontal areas were activated in relation to eye movement in normal subjects during eye opening but not during eye closing. While persistent interictal spike and wave activity was present over the posterior and anterior scalp in the patient upon eye closing, f-MRI showed bilateral activation of the parietal and temporal regions. This fMRI study documents the activation of posterior and temporal areas related to continuous intercritical spikes evoked by eye closure, which are diffuse over the scalp. This activation was absent in the control group during eye closure.

Continuous EEG-fMRI in Pre-Surgical Evaluation of a Patient with Symptomatic Seizures: Bold Activation Linked to Interictal Epileptic Discharges Caused by Cavernoma.

We used continuous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the linkage between the "epileptogenic" and the "irritative" area in a patient with symptomatic epilepsy (cavernoma, previously diagnosed and surgically treated), i.e. a patient with a well known "epileptogenic area", and to increase the possibility of a non invasive pre-surgical evaluation of drug-resistant epilepsies. A compatible MRI system was used (EEG with 29 scalp electrodes and two electrodes for ECG and EMG) and signals were recorded with a 1.5 Tesla MRI scanner. After the recording session and MRI artifact removal, EEG data were analyzed offline and used as paradigms in fMRI study. Activation (EEG sequences with interictal slow-spiked-wave activity) and rest (sequences of normal EEG) conditions were compared to identify the potential resulting focal increase in BOLD signal and to consider if this is spatially linked to the interictal focus used as a paradigm and to the lesion. We noted an increase in the BOLD signal in the left neocortical temporal region, laterally and posteriorly to the poro-encephalic cavity (residual of cavernoma previously removed), that is around the "epileptogenic area". In our study "epileptogenic" and "irritative" areas were connected with each other. Combined EEG-fMRI may become routine in clinical practice for a better identification of an irritative and lesional focus in patients with symptomatic drug-resistant epilepsy.

Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy: a combined transcranial magnetic stimulation and EEG study.

OBJECTIVE: To investigate the effect of sleep deprivation on corticospinal excitability in patients affected by juvenile myoclonic epilepsy (JME) using different transcranial magnetic stimulation (TMS) parameters. METHODS: Ten patients with JME and 10 normal subjects underwent partial sleep deprivation. Motor threshold (MT), motor evoked potential amplitude (MEP), and silent period (SP) were recorded from the thenar eminence (TE) muscles. Short latency intracortical inhibition (SICI) and short latency intracortical facilitation (SICF) were studied using paired magnetic stimulation. TMS was performed before and after sleep deprivation; EEG and TMS were performed simultaneously. RESULTS: In patients with JME, sleep deprivation induced a significant decrease in SICI and an increase in SICF, which was associated with increased paroxysmal activity. A significant decrease in the MT was observed. No significant changes in any TMS parameters were noted in normal subjects after sleep deprivation. The F wave was unchanged by sleep deprivation in both control subjects and in patients with JME. CONCLUSIONS: In patients with JME, sleep deprivation produces increases in corticospinal excitability in motor areas as measured by different TMS parameters.

Cutis verticis gyrata, mental retardation and Lennox-Gastaut syndrome: a case report.

Cutis verticis gyrata (CVG) is an abnormality of the scalp characterized by the formation of furrows and folds which cannot be flattened by traction or pressure. Primary and secondary forms of CVG have been described. We report on a patient affected by cutis verticis gyrata, mental regression and Lennox-Gastaut syndrome (LGS). Serum hormonal levels, karyotype and X fragile studies were normal. Magnetic resonance imaging of the brain showed only atrophic changes. The etiology of primary CVG remains unknown as does its relation with LGS.

Early and late intracortical inhibition in juvenile myoclonic epilepsy.

PURPOSE: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy. METHODS: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIs) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits. RESULTS: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age-matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period. CONCLUSIONS: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.

Painless fractures and thermoregulation disturbances in sensory-autonomic neuropathy: electrophysiological abnormalities and sural nerve biopsy.

We describe the case of a young girl suffering from thermoregulation disturbances, painless fractures and arthropathy since early childhood. The patient was diagnosed as having a hereditary sensory autonomic neuropathy. Although needle EMG, conventional nerve conduction studies and somatosensory evoked potentials gave normal results, sympathetic skin responses (SSRs) were absent. Sural nerve biopsy showed a substantial reduction in the number of small myelinated and unmyelinated fibers. We emphasize the importance of SSR testing in revealing a condition which is otherwise difficult to identify by electrophysiological techniques. The combined evidence of functional and morphological findings is strongly suggestive of selective peripheral nerve involvement.

Sympathetic skin response asymmetry in early stage idiopathic Parkinson's disease.

Simultaneous bilateral plantar sympathetic skin response (SSR) was studied in 25 patients with early stage idiopathic Parkinson's disease (IPD), characterized by monolateral motor involvement (Hoehn and Yahr, stage <2) and without clinical evidence of autonomic dysfunctions. Thirteen (mean age: 68.69 +/- 7.70, range 55-76) had extrapyramidal clinical signs only at the left body side, 12 (mean age 66.60 +/- 7.43, range 51-73) at the right body side. A group of 25 healthy, age-matched, subjects were also evaluated. To evoke the responses, trains of 10 electrical pulses were applied at different intensities and frequencies. Only intensities of stimulation > or = 5 times the sensory electrical threshold always assured bilateral plantar responses in all the examined subjects. Amplitude asymmetry between left and right responses was found only in the IPD patients (P < 0.05). The amplitude reduction corresponded to the motor affected side. No analogue latency variation was observed in any group. Independently from the peripheral or central origins of such phenomena, these findings suggest that simultaneous bilateral SSR amplitude evaluation could be useful, in early IPD patients, to demonstrate and to monitor the sympathetic cholinergic dysfunction, despite the lack of autonomic symptoms.

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

PURPOSE: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment. METHODS: We investigated single-pulse TMS in six patients with complex partial seizures. The TMS recordings were performed in five sessions before and during 5 weeks of treatment. Motor threshold, motor-evoked potential (MEP) amplitude, cortical silent period, and peripheral conduction velocity were used as parameters of evaluation. LTG was started with a dosage of 25 mg/day until a daily maintenance dosage of 200 mg/day was reached. RESULTS: The motor threshold activation of thenar muscles was significantly increased by LTG after 2 weeks of treatment and was increased in a parallel way to the loading dose of the drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles did not show significant changes at high- or low-intensity stimulation. The cortical silent period remained unchanged at low- and high-intensity stimulation. The absolute latency of MEPs after cortical and cervical stimulation was unchanged, as was the central motor conduction time. CONCLUSIONS: Our study documents that loading doses of LTG, administered as monotherapy, progressively increases patients' motor thresholds over short periods.

Mechanism of binocular interaction in refraction errors: study using pattern-reversal visual evoked potentials.

In this study we sought to determine whether a natural condition involving fine discrimination, for example moderately severe myopia, might yield interesting information regarding the binocular interaction expressed by visual evoked potentials (VEPs). We studied ten normal subjects with a mild refraction deficits. Transient VEPs were elicited by monocular and binocular stimulation under conditions of natural and lens-corrected vision. The visual stimulus was a pattern-reversal checkerboard consisting of 15' and 40' checks. VEPs in response to binocular stimulation were compared with monocular VEPs. We plotted the monocular 'better-VEP' and 'worse-VEP' response, since significant differences between individual eye stimulations were present. We found no significant difference between the mean N75 and P100 latencies of the binocular VEP and the better monocular VEP, regardless of the check size used and of natural or corrected vision. Under all stimulus conditions, the mean amplitude of the N75-P100 of the binocular VEPs was also larger than the better monocular VEP response. The difference proved more significant when we stimulated our subjects with smaller squares and left vision uncorrected. The mean P100-N145 amplitude obtained with binocular stimulation was larger than the better monocular VEP response only when using small checks (15') and uncorrected vision. Overlapping latencies are consistent with an earlier hypothesis that monocular and binocular VEPs originate postsynaptically from the binocular neurons in the primary visual cortex. The gain in amplitude achieved by binocular stimulation may depend upon the removal of 'tonic interocular inhibition' and/or on a cortical modulatory mechanism.

Eclamptic encephalopathy: imaging and pathogenetic considerations.

Eclampsia is a rare condition peculiar to pregnant and puerperal women, characterized by clinical pre-eclampsia (hypertension, proteinuria, edema) and generalized seizures. Three cases of eclamptic encephalopathy are reported: CT and MRI demonstrated transient abnormalities in the cortical and subcortical regions of the posterior areas of the brain - namely, parieto-occipital lobes - associated with occasional involvement of basal ganglia and/or brainstem. Pathogenesis is still unclear. Strict similarity with the pathological findings characterizing hypertensive encephalopathy suggests that a focal impairment in cerebral autoregulation may be the cause of vasodilation and fluid extravasation leading to hydrostatic edema; selective involvement of posterior areas could be explained by their lesser degree of adrenergic innervation supporting circulatory autoregulation mechanisms.

Binocular interaction in normal vision studied by pattern-reversal visual evoked potential (PR-VEPS).

Monocular and binocular visual evoked potentials (VEPs) in response to different check size (15-21-38-84 minutes or arc) were studied in 14 subjects with normal visual acuity and stereopsis. The binocular VEP amplitude is slightly higher than the VEP amplitude on stimulation of the "better eye" and significantly higher than the VEP amplitude on stimulation of the "worse eye"; this effect is observed using small checks and almost exclusively involved N75-P100. Both the N75 and P100 peaks occur earlier after binocular than monocular stimulation. The shortening of the N75 mean latency is significantly greater than that of the P100 mean latency when larger check sizes are used. The mean latency of the N145 potential is not significantly different in monocular and binocular stimulus conditions. The slight summation effect and latency shortening in the binocular VEPs are not consistent with the hypothesis that it is the sum of separate monocular signals originating from the visual cortex that gives rise to the response. The early components of both monocular and binocular VEPs are thought to be of post-synaptic origin (outside layer 4c of area 17), where the inputs become mixed so that most cells receive information from both eyes. The amplitude enhancement of binocular VEPs, which mainly occurs when using small checks, may be related to the increase in the total amount of cortical activity representing the macular region; this may account for binocular superiority in fine spatial resolution. The latency shortening in binocular conditions can be explained by considering that the critical determinant of the latency is the fundamental spatial frequency of the pattern. When coarse patterns are used, their effectiveness in parafoveal stimulation may affect the VEPs, with a significant contribution coming from the more peripheral retina. The enlargement of the visual field when the eyes see simultaneously may therefore further reduce the latency of the response when using the larger checks suitable for eccentric stimulation.

Comparative assessment of peripheral sympathetic function by postural vasoconstriction arteriolar reflex and sympathetic skin response in NIDDM patients.

PURPOSE: The aim of the study was to compare peripheral sympathetic adrenergic and cholinergic nerve function in NIDDM (non-insulin-dependent diabetes mellitus) patients with various degrees of diabetic neuropathy and neuropathic foot ulceration. The parameters used were postural vasoconstriction arteriolar reflex (VAR) and sympathetic skin response (SSR), respectively. PATIENTS AND METHODS: Forty-seven NIDDM patients were studied. No patients had clinically significant peripheral vascular disease. They were divided according to peripheral somatic neuropathy, assessed by clinical score and vibration perception threshold (VPT). Twenty-two patients showed no significant evidence of peripheral neuropathy and normal VPT (DN-); 15 had signs and symptoms of neuropathy and VPT alteration (DN+); 10 had diabetic neuropathy and foot ulceration (DNU). Twenty-two normal subjects were also examined as a control group. Resting arteriovenous shunt skin blood flow, measured using laser-Doppler flowmetry, and the VAR of the big toe on lowering the foot were studied. Sympathetic skin response was assessed by an EMG apparatus. Autonomic function was also investigated by using standard cardiovascular reflex tests. RESULTS: Resting blood flow values were similar in the three NIDDM groups and in the control group. VAR to foot lowering was significantly impaired in all NIDDM groups by comparison with controls (72.8 +/- 2.1%, mean +/- SEM), this impairment being progressively more pronounced in DN- (58.8 +/- 2.3%, P < 0.001), DN+ (33.3 +/- 3.0%, P < 0.001 versus DN-) and DNU (8.6 +/- 2.7%, P < 0.001 versus DN+). Sympathetic skin response was assessed in 28 patients and was significantly impaired in DN-compared with the control group (2.53 +/- 0.04 versus 2.71 +/- 0.04 log mcV, P < 0.01). This impairment was severe in the DNU compared with the DN+ group (1.36 +/- 0.05 versus 2.26 +/- 0.04 log mcV, P < 0.005). A positive correlation was found between VAR values and SSR (P < 0.001), and these measurements were also closely correlated with several parameters of central autonomic and somatic neuropathy. CONCLUSION: These results indicate that peripheral sympathetic adrenergic and cholinergic fibers simultaneously undergo early alterations in diabetic patients, even when there is no clinical neuropathy. Our data also show almost complete abolition of peripheral sympathetic activity in NIDDM patients with foot ulceration.

Botulinum toxin treatment of muscle cramps: a clinical and neurophysiological study.

Botulinum toxin is now widely used in the treatment of several hyperkinetic movement disorders. To evaluate its efficacy in treating muscle cramping syndromes, we studied clinical and neurophysiological variables before and after botulinum toxin injections into calf muscles and small flexor muscles of the foot in patients with an inherited benign cramp-fasciculation syndrome. At each assessment the clinical severity of cramp was scored and the cramp threshold frequency was measured with repetitive electrical peripheral nerve stimulation. Botulinum toxin injection significantly lowered our patients' clinical cramp severity scores (mean +/- SD: before, 3.80 +/- 0.44; after, 1.40 +/- 0.54), left muscle strength unchanged and significantly increased their cramp threshold frequencies (before, 4.22 +/- 2.26 Hz; after, 10.0 +/- 3.74 Hz). The clinical benefit induced by botulinum toxin lasted about 3 months. Botulinum toxin injections also significantly reduced fasciculation potentials in relaxed muscles (before, 0.86 +/- 0.19 fasciculations/sec; after, 0.45 +/- 0.11 fasciculations/sec). These findings show that local intramuscular injections of botulinum toxin provide effective, safe, and long-lasting relief of cramps possibly by reducing presynaptic cholinergic stimulation of motor nerve terminals and by impairing the input/output function of intrafusal and extrafusal motor end plates.

Reduced servo-control of fatigued human finger extensor and flexor muscles.

1. In healthy human subjects holding the index finger semi-extended at the metacarpophalangeal joint against a moderate load, electromyographic (EMG) activity was recorded from the finger extensor and flexor muscles during different stages of muscle fatigue. The aim was to study the effect of muscle fatigue on the level of background EMG activity and on the reflex responses to torque pulses causing sudden extensor unloadings. Paired comparisons were made between the averaged EMG and finger deflection responses under two conditions: (1) at a stage of fatigue (following a sustained co-contraction) when great effort was required to maintain the finger position, and (2) under non-fatigue conditions while the subject tried to produce similar background EMG levels to those in the corresponding fatigue trials. 2. Both the unloading reflex in the extensor and the concurrent stretch reflex in the flexor were significantly less pronounced and had a longer latency in the fatigue trials. Consequently, the finger deflections had a larger amplitude and were arrested later in the fatigue trials. 3. It is concluded that--with avoidance of 'automatic gain compensation', i.e. reflex modifications attributable to differences in background EMG levels--the servo-like action of the unloading and stretch reflexes is reduced in fatigued finger extensor and flexor muscles.

After-effects on stiffness and stretch reflexes of human finger flexor muscles attributed to muscle thixotropy.

1. While the subject maintained a weak contraction in his finger flexor muscles, holding the metacarpophalangeal joints in 45 deg flexion, test torque pulses were applied which caused rapid finger extension movements and electromyographic (EMG) stretch reflex responses. Before each test pulse the fingers were passively flexed or extended ('post-short' and 'post-long' trials) for about 10 s. The EMG and joint deflection responses in the two types of trial were compared after averaging. 2. In the 'post-long' trials, the EMG reflex response showed a comparative increase in latency, with a reduction of the short-latency (M1) component and an enhancement of the medium-latency (M2) component. 3. The angular deflections were larger, and the turning points of the deflections, which indicated the start of the mechanical reflex responses, occurred later in the 'post-long' trials. These differences were not seen when the torque pulse was immediately preceded by a strong, brief isometric finger flexor contraction in the test position. 4. Immediately following the return to the test position the background finger flexor EMG activity was larger in the 'post-long' trials, a difference which gradually subsided over 15-20 s. A strong, brief contraction in the test position also eliminated this inter-trial difference. 5. The results are interpreted as manifestations of thixotropic after-effects in intra- and extrafusal muscle fibres. It is proposed that the M1 component of the stretch reflex is largely a response to the 'initial burst' of impulses in primary spindle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of tibial nerve early cortical potentials in normal subjects.

The aim of the study was to calculate and test the variability of several tibial nerve SEP parameters, particularly scalp amplitude distribution, with a view to obtaining more reliable clinico-electrophysiological correlations. The parameters were evaluated in 20 healthy subjects using a simple, easily reproducible recording method. The absolute latency of the P40 wave was greater than that of the N37 wave, except in two cases. Paradoxical lateralization was present in all subjects. On the basis of the scalp amplitude distribution of the ipsi- and contralateral potentials, three distinct groups were identified: a) dominance of ipsilateral P40, 29 sides; b) dominance of P37, 15 sides; and c) equivalent amplitude of P37 and ipsilateral P40, 5 sides. The individual amplitude values of these potentials were plotted on a normogram. The results suggest that (i) the absence of one or more early cortical SEPs may be considered abnormal; (ii) when SEP scalp lateralization is present, it may be useful to compare the amplitude distribution of the individual components in normal and pathological populations; and (iii) for this purpose, lateralized potentials are more reliable owing to their lower degree of amplitude dispersion.

The influence of muscular lengthening on cramps.

Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contraction or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hypothesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism.