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.

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.

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.

Multifactorial etiological aspects of epilepsy.

The results of a computerized analysis of 555 newly recognized idiopathic epilepsy patients (301 males and 254 females) are presented. All patients were under 30 years over the period 1980-1985. The possible prenatal and perinatal risk factors (RFs) for epilepsy were investigated. The data showed that 307 patients (55.5%) had possible RFs; 162 had one possible RF, 145 two or more. The association of two or more RFs had a high frequency in secondary generalized epilepsy (66.6%) and in partial epilepsy. A multifactorial etiology of epilepsy is suggested, hypothesizing a connection either between prenatal and perinatal RFs or between multiple perinatal RFs.

Assessment of autonomic functions in insulin-dependent diabetic children and adolescents.

Autonomic function has been studied in 30 insulin-dependent diabetic children and adolescents, through five cardiovascular tests. A significant difference between the diabetic and the control subjects was found in heart rate variations after deep breathing and after standing. Fifty percent of our patients showed an altered response to one or more cardiovascular tests. Although clinical manifestations of autonomic dysfunction are not frequent in young insulin-dependent patients, early signs of functional alterations are detectable in a high percentage of them.

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.

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.

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.

Tonic vibration reflexes elicited during fatigue from maximal voluntary contractions in man.

1. In the present study on human foot dorsiflexor muscles we have examined the effects of high-frequency (150 Hz) muscle vibration on weak or moderate voluntary contractions (maintained by constant effort) and on maximal voluntary contractions (MCVs) of (i) non-fatigued muscles, (ii) muscles fatigued by sustained MVCs and (iii) muscles deprived of gamma-fibre innervation by partial anaesthetic nerve block. The motor outcome of the voluntary dorsiflexion efforts was assessed by measuring the firing rates of single motor units in the anterior tibial (TA) muscle, the mean voltage EMG activity from the pretibial muscles and foot dorsiflexion force. 2. With the subject instructed to exert constant effort in maintaining a weak or moderate contraction, superimposed vibration caused an enhancement of EMG activity and contraction force. 3. Previous claims that muscle vibration has no facilitatory effect on motor output in MVCs were found to hold true for non-fatigued but not for fatigued muscles. Thus, the fatigue-induced decline in EMG activity and motor unit firing rates was counteracted by short periods (less than 10-20 s) of superimposed vibration. However, with longer vibration periods it seemed as if the initial facilitation converted into an opposite effect which accentuated the fatigue-induced decline in motor output and contraction force. 4. Like muscle fatigue, a partial anesthetic block of the deep peroneal nerve, supposedly interrupting transmission in gamma-motor fibres, caused a reduction of MVC motor unit firing rates which could be counteracted by muscle vibration. In prolonged MVCs performed during the block, motor unit firing rates did not show the normal progressive decline from an initially high level, but stayed at a relatively constant low level throughout the contraction period. 5. Even though alternative interpretations are possible, the results agree with the hypotheses (i) that in sustained MVCs, fatigue processes occur not only in extrafusal but also in intrafusal muscle fibres, (ii) that the intrafusal fatigue leads to a reduction of the voluntary drive conveyed to the alpha-motoneurones via the gamma-loop and (iii) that vibration-induced activity in group Ia afferents can act as a substitute for the diminished fusimotor drive.

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.

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)

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.

Prolonged muscle vibration reducing motor output in maximal voluntary contractions in man.

1. We observed in a previous study on the human foot dorsiflexor muscles that the fatigue-induced decline in motor output during sustained maximal voluntary contractions (MVCs) was temporarily counteracted during the initial phase of superimposed high-frequency (150 Hz) muscle vibration, whereas prolonged muscle vibration seemed to accentuate the fatigue-induced decline in gross EMG activity and motor unit firing rates. A more extensive investigation of this late effect of muscle vibration on MVCs was performed in the present study. 2. Prolonged periods of superimposed muscle vibration caused a reduction of EMG activity, motor unit firing rates and contraction force in both intermittent and sustained MVCs. This vibration-induced effect had the following main characteristics: (i) it developed slowly during the course of about 1 min of sustained vibration and subsided within 10-20 s after the end of vibration; (ii) it was much more pronounced in some subjects than in others (not age-dependent) and it was accentuated by preceding muscle exercise; (iii) it affected primarily the subject's ability to generate and/or maintain high firing rates in high-threshold motor units. 3. Since the effect developed while vibration at the same time exerted a tonic excitatory influence on the alpha-motoneurone pool (as evidenced by the presence of a tonic vibration reflex) it is argued that the vibration-induced suppression of motor output in MVCs probably does not depend on alpha-motoneurone inhibition, but on a reduced accessibility of these neurones to the voluntary commands. It is suggested that contributing mechanisms might be vibration-induced presynaptic inhibition and/or 'transmitter depletion' in the group Ia excitatory pathways which constitute the afferent link of the gamma-loop.

Acute peroneal compartmental syndrome. Report of a case.

Among the compartmental syndromes the necrosis of peroneal muscles is unusual. We report a case in which the swelling of peroneal muscle causes a compression of the common peroneal nerve below the peroneal head. A disturbance of both the motility and sensibility of the deep and superficial peroneal nerve is present with different pathogenesis. In fact, EMG suggested a muscular damage of the peroneal compartment and a denervation of the pretibial muscle. Interfascicular neurolysis along the peroneal nerve was performed to decompress the common and the deep peroneal nerve. A recovery in the territory of the tibialis anterior deep peroneal nerve confirmed the different mechanisms of paralysis.

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.

Congenital muscular dystrophy and cerebellar vermis agenesis in two brothers.

Two brothers with motor retardation since the first months of life presented waddling ataxic-gait with lumbar lordosis, joint contractures and generalized muscle weakness. Both presented altered cerebellar tests and scanning speech. Creatine kinase, electromyography (EMG) and muscle biopsy pointed to muscular disease while CT scanning and NMR imaging showed cerebellar vermis agenesis. On this evidence we diagnosed the unusual association of vermian agenesis and congenital muscular dystrophy.