Postural responses to low-intensity, short-duration, galvanic vestibular stimulation as a possible differential diagnostic procedure.

OBJECTIVES: In this study we investigated the effect of polarity-related differences in short-duration very low-intensity galvanic vestibular stimulation (GVS), not perceived by the subject, by evaluating the minimal postural sway responses in healthy people. We also verified its possible usefulness as a differential diagnostic tool in patients with postural instability disturbances related to polyneuropathy or peripheral vertigo. METHODS: We applied bimastoid opposite polarity direct current GVS (0.7 mA for 1 s) and recorded the induced postural response with an electromagnetic head position tracker. Latency, amplitude, velocity and an asymmetry index were measured between two reverse polarity sessions. RESULTS: The postural response was easily recorded and was statistically wider in amplitude and velocity in the polyneuropathy group than in the other groups. Postural responses were asymmetric only in the group with mild peripheral vertigo. CONCLUSION: These findings suggest that even weak GVS affects vestibular excitability: cathodal polarization increases whereas anodal GVS decreases excitability. Symmetry and amplitude or velocity of the postural responses, particularly in the eyes closed condition, can differentiate the three groups of subjects tested.

Combined transcranial Doppler and EEG recording in vasovagal syncope.

BACKGROUND: In neurally mediated syncope a 'typical' EEG pattern during hyperventilation (HV) may be observed. This study aimed to investigate transcranial Doppler (TCD) and EEG variations in response to hyper- and hypocapnia using simultaneous recording. METHODS: Syncope patients with a typical EEG pattern during HV (SEEG+, n = 15) and those without abnormalities (SEEG-, n = 16) were compared with healthy controls (n = 20). Simultaneous TCD and EEG recordings were performed at rest (baseline), during 2 apnea tests and during HV. Cerebrovascular vasoreactivity, index for hypocapnia, total vasomotor reserve and time to flow velocity normalization after HV (t-norm) were recorded. RESULTS: With TCD, a reduction in Vasomotor reserve was observed in SEEG+ compared with the other 2 groups (control: 67 +/- 8%; SEEG-: 67 +/- 10%; SEEG+: 57 +/- 8%; p < 0.0001). t-norm was longer in all syncopal patients and in particular in SEEG+ (control: 20.2 +/- 3 s; SEEG-: 40 +/- 7 s; SEEG+: 123 +/- 45s; p < 0.0001). Quantitative EEG showed an increase in slow bands in all subjects during HV, small and nonsignificant in controls and SEEG-, higher and significant in SEEG+, related with flow reduction. CONCLUSIONS: Changes in the sympathetic modulation of cerebral vasoconstriction may explain both the pathophysiology of vasovagal syncope and the typical paroxysmal EEG findings.

Chromatic modulation of luminance visual evoked potential latencies in healthy subjects and patients with mild vision disorders.

OBJECTIVE: To study whether and how color modulates luminance visual evoked potentials (VEPs). METHODS: We studied pattern-reversal luminance VEPs to red/black and blue/black checkerboards with identical luminance contrast values (mixed luminance and chromatic components) (isocontrast color VEP, in brief, IVEPs) in 25 healthy subjects and two groups of patients with mild vision disorders (23 with glaucoma and 25 with optic neuritis). We then compared these with the standard color VEPs to pure chromatic contrast red/green and blue/yellow gratings (CVEPs). RESULTS: In healthy subjects, VEPs to red/black checkerboards and red/green gratings were slower than those obtained with blue/black checkerboards and blue/yellow gratings. Both procedures (IVEPs and CVEPs) differentiated patients with vision disorders from healthy subjects and distinguished between the two different vision disorders. Red/black checkerboards and red-green gratings elicited slower VEPs in patients with optic neuritis and blue/black checkerboards and blue/yellow gratings elicited slower VEPs in patients with glaucoma. IVEPs appeared more stable and ample than CVEPs. The contrast indices normalized CVEP and IVEP latencies in the same subject and showed a positive correlation between CVEP and IVEP latencies in healthy subjects and in patients with optic neuritis, but not in patients with glaucoma. CONCLUSIONS: Our study confirms the usefulness of CVEPs in detecting and differentiating mild vision disorders. IVEPs to colored pattern-reversal luminance checkerboards are equally effective in distinguishing between various vision disorders possibly because colors can modulate VEP latencies to luminance contrast stimuli. SIGNIFICANCE: IVEPs can be useful in differentiating the various vision disorders and are easier than CVEPs to test in a routine clinical setting.

Fast voluntary neck movements in patients with cervical dystonia: a kinematic study before and after therapy with botulinum toxin type A.

OBJECTIVE: To study fast voluntary neck movements in patients with cervical dystonia (CD) before and after therapy with botulinum toxin type-A (BTX-A). METHODS: A selected sample of 15 patients with CD (with prevalent torticollis) and 13 age-matched control subjects performed both right and left rotational, and flexion and extension neck movements as fast as possible. Movements were recorded with a motion analysis system (SMART, BTS). Movement time, angular amplitude, and peak angular velocity were analyzed. In patients, rotational neck movements were pooled as "pro-dystonic" (toward the dystonic side) and "anti-dystonic" (toward the non-dystonic side). Results obtained in patients before BTX-A treatment were compared with those of control subjects. The effect of BTX-A treatment was evaluated by comparing movement performance before and after treatment. RESULTS: Before receiving BTX-A, patients performed pro- and anti-dystonic movements with lower peak angular velocity than control subjects. Pro-dystonic movements had a reduced angular amplitude. Anti-dystonic movements showed an abnormally long movement time. Flexion and extension movements required longer movement times, but the other kinematic variables were normal. After BTX-A injections, pro-dystonic movement amplitude and anti-dystonic movement peak angular velocity increased, whereas flexion and extension movements remained unchanged. CONCLUSIONS: Before BTX-A injection patients with CD perform fast voluntary neck movements abnormally and BTX-A injections improved their peak velocity and amplitude. SIGNIFICANCE: Kinematic studies can detect specific neck movement disturbance in patients with CD, and can quantify both the severity of clinical picture and the effect of BTX-A injections in these patients.

Luminance and chromatic visual evoked potentials in type I and type II diabetes: relationships with peripheral neuropathy.

The objective of the study was to investigate the subclinical visual deficit in type I and II diabetes, and its relationship with peripheral neuropathy. Thirty-two healthy volunteers, 20 patients with type I diabetes and 30 patients with type II diabetes were studied in a clinical neurophysiology setting. Luminance (VEPs) and chromatic visual evoked potentials (CVEPs) were recorded, with white-black, grey-black, red-green and blue-yellow sinusoidal gratings. The peak latencies of the VEP positive wave and CVEP negative wave were recorded. Ten patients with type I and 8 with type II diabetes had peripheral neuropathy. VEPs were slower in patients with type II diabetes and CVEPs were slower in patients with type I and type II diabetes than in controls. Blue-yellow CVEPs were slower in type II than in type I diabetes. VEPs and red-green CVEPs were slower in patients with diabetes with neuropathy than in those without. In conclusion, we found that visual system impairment differs in diabetes with and without peripheral neuropathy.

Effects of repetitive transcranial magnetic stimulation in a patient with fixation-off sensitivity.

Aim of the present study was to evaluate the acute and long-term effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on focal epileptiform interictal EEG activity in a patient with fixation-off sensitivity and partial epilepsy. Real and sham rTMS were delivered over the vertex. Two trains of 500 stimuli per day were delivered at 0.33 Hz frequency and threshold intensity for five consecutive days. The number of posterior EEG spikes and spike-and-wave complexes/min before and after the application of rTMS were compared in a blinded manner. In our patient, real-rTMS induced a long-lasting decrease in the number of posterior EEG spikes and spike-and-wave complexes/min. Despite the limitations of a single case report, our study confirms that low-frequency rTMS significantly reduces interictal focal epileptic activity over time.

Observations on EEG patterns in neurally-mediated syncope: an inspective and quantitative study.

We performed an observational EEG study in 43 patients with neurally-mediated syncope in basal condition and during hyperventilation (HV), and compared it with 32 healthy controls. On blind analysis at rest, EEG was classified as normal in 47% of patients (vs. 94% of controls, P < 0.001). More abundant and pronounced delta-theta activities and alpha slowing were found in patients than in control subjects on both visual inspection and quantitative spectral analysis. During prolonged HV, the EEG remained normal in 21% of patients only. Slow activities became more evident in patients than in control subjects, and intermittent rhythmic delta activity appeared in 40% of syncopal patients. These "pseudoparoxysmal" EEG changes differed from the common slowings induced by HV in adult subjects and were not observed in our control subjects. Moreover, these distinctive EEG changes, a common finding in syncopal patients, could not be confused with epileptiform activity of any kind. Further studies will clarify the pathophysiology of these EEG modifications.

Surface electromyography and mechanomyography recording: a new differential composite probe.

The objective of the study was to develop a new surface probe for differential mechanomyographic (MMG) and electromyographic (EMG) recording. Differential amplification is commonly used in electromyography to improve the signal-to-noise ratio. A new composite probe was developed with two electrodes (EMG) and two identical piezo-electric membranes (MMG) to be positioned on muscle. The probe had two built-in fixed-gain differential amplifiers: one to amplify the electric signal and the other to amplify the vibration signal. A similar non-differential MMG probe was used for comparisons. Burst muscular activity was recorded using the non-differential and differential probes and was used to test the performance of the two probes in suppressing artifacts of non-muscular origin. Power spectrum analysis of signals from the two probes showed that differential amplification significantly improved the signal-to-noise ratio in MMG recordings and significantly suppressed artifacts (power difference > 90%). The composite probe allowed simultaneous differential recording of MMG and EMG signals from the same muscular site. It recorded muscular activity more efficiently than the non-differential probe and could therefore be useful in studying fatigue and neuromuscular diseases.

Autoantibodies to glutamic acid decarboxylase in downbeat nystagmus.

The cause of downbeat nystagmus (DBN) remains undiagnosed in about 40% of patients. This paper reports the presence of antiglutamic acid decarboxylase antibodies (GAD-Ab) in a patient with DBN. Antibodies against GABAergic neurons located in the vestibular complex may induce chemical denervation of the floccular neurons, which normally suppress the peripheral imbalance between vertical semicircular canal systems, thereby causing DBN. Testing for GAD-Ab may be indicated in DBN patients without an identifiable anatomical brain lesion.

Video color perimetry: impairment in glaucoma suspects.

PURPOSE: To detect mild visual field impairment in asymptomatic glaucoma suspect patients. METHODS: Color perception within the visual field was tested with customized color video perimetry. The key features of the system were stimuli color desaturation, low-level luminance and equiluminant gray background. Twenty patients with asymptomatic glaucoma were tested and compared with a group of age-matched control subjects. RESULTS: Automated perimetry test findings differed significantly in the two groups, particularly for short-wavelength sensitivity (blue). The severity of color impairment correlated directly with intraocular pressure. CONCLUSION: Desaturated low-luminance video perimetry will reliably detect and quantify asymptomatic visual field defects. A previous work on multiple sclerosis has detected a mild long-wavelength (red) impairment in asymptomatic patients after an episode of optic neuritis, even in clinically unaffected fellow eyes. Our findings in glaucoma suspect patients indicate that a mild blue impairment could be the initial sign of this disease.

Clinical and electroencephalographic effects of topiramate in patients with epilepsy and healthy volunteers.

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.

Changes in color vision after a single dose of vigabatrin or carbamazepine in healthy volunteers.

In patients with epilepsy the older antiepileptic drugs induce distinct electroencephalographic changes and may also alter visual function. Although the effects of the newer antiepileptic drugs on the electroencephalogram remain less clear, long-term treatment with vigabatrin (VGB) has been reported to induce severe and permanent visual impairment. Our aim in this study was to investigate the effects of a single oral dose of VGB and carbamazepine (CBZ) on visual function in normal healthy volunteers randomly assigned to three groups according to a single-blind, placebo-controlled design. All subjects underwent color visual evoked potential tests and color perimetry at baseline and after receiving placebo, VGB (2,000 mg) or CBZ (400 mg). Whereas CBZ induced a mild overall impairment of the chromatic and achromatic systems, VGB induced a selective blue impairment. The differential changes the two antiepileptic drugs induced in visual tests presumably depend on their different mechanisms of action. The selective blue impairment in color visual tests in VGB-treated healthy subjects is consistent with gamma-aminobutyric acid (GABA)-ergic inhibition also at retinal level. Hence, color visual tests may be suitable to detect initial visual abnormalities in VGB-treated patients with epilepsy.

Sympathetic skin response and cardiovascular autonomic function tests in Parkinson's disease and multiple system atrophy with autonomic failure.

The relationship between sympathetic skin response (SSR) and cardiovascular autonomic function tests (CVTs) was investigated in 15 patients with idiopathic Parkinson's disease (PD), 15 patients with clinical evidence of multiple system atrophy (MSA) with autonomic failure, and in 15 healthy control subjects. SSR was elicited by electrical stimulation of the right and left median nerves and simultaneously recorded on the palms of both hands. CVTs included the following sympathetic and parasympathetic tests: orthostatism, head-up tilt, cold pressor test, deep breathing, Valsalva maneuver, and hyperventilation. The SSR was normal in all patients with PD and control subjects but was abnormal or absent in all patients with MSA. For patients with MSA, SSR latency was significantly longer and amplitude was significantly smaller than that of patients with PD and control subjects. For patients with PD, SSR did not differ from that of control subjects. In these patients, SSR latency was significantly longer and SSR amplitude was smaller when the side with more marked motor symptoms was stimulated, both ipsilaterally and contralaterally to the side of stimulation. A statistically significant difference in SSR latencies and amplitudes was found between patients with PD and control subjects only when motor asymmetries were considered. CVTs showed severe sympathetic and parasympathetic hypofunction in patients with MSA, but not in patients with PD or control subjects. No correlation was found between SSR and CVTs that assess sympathetic function in patients and control subjects. SSR is indicated as an additional test for the evaluation of sympathetic degeneration in patients with MSA.

A new color vep procedure discloses asymptomatic visual impairments in optic neuritis and glaucoma suspects.

OBJECTIVE: To evaluate the reliability of visual evoked potentials obtained with a set of multiple chromatic and achromatic patterns (C-VEPs) in differentiating asymptomatic perifoveal retinal impairment from central conduction impairment. METHODS: We propose a set of colored pattern stimuli that allows relatively differential activation of the magnocellular and parvocellular pathways. The system runs on a standard Pentium PC with peripherals that present stimuli and collect, analyze and print data. P1 latencies of C-VEPs obtained with achromatic (black/white) and chromatic (blue/black and red/black isocontrast) checkerboards were evaluated in normal subjects and patients with subclinical retinal impairment (glaucoma suspects) or mild neural conduction impairment (optic neuritis), none of whom had subjective visual defects. RESULTS: The procedure evoked robust cortical signals and statistically distinguished the 3 groups of subjects. The achromatic and chromatic stimuli used distinguished controls from glaucoma suspects and patients with optic neuritis. Glaucoma suspects had greater impairment of C-VEPs to blue/black checkerboards whereas patients with optic neuritis had greater impairment of responses to red/black stimuli. CONCLUSIONS: Our data suggest that chromatic patterns (color/ black, red and blue), that may activate the parvocellular and magnocellular systems differentially but not selectively, can distinguish between mild perifoveal or foveal conduction impairment. They have the additional advantage of evoking large, stable responses across all the subjects.

Three-dimensional mapping of brainstem functional lesions.

The human brainstem is a highly complex structure where even small lesions can give rise to a variety of symptoms and outward signs. Localising the area of dysfunction within the brainstem is often a difficult task. To make localisation easier, a neural net system has been developed which uses 72 clinical and neurophysiological data inputs to provide a display (using 5268 voxels) on a three-dimensional model of the human brainstem. The net was trained by means of a back-propagation algorithm, over a pool of 580 example cases. Assessed on 200 test cases, the net correctly localised 83.6% of the target voxels; furthermore the net correctly localised the lesions in 31 out of 37 patients. Because this computer-assisted method provides reliable and quantitative localisation of brainstem areas of dysfunction and can be used as a 3D interactive functional atlas, it is expected to prove useful as a diagnostic tool for assessing focal brainstem lesions.

Localisation of a reporter transcript by the c-myc 3'-UTR is linked to translation.

The 3'-untranslated region of c-myc mRNA contains a perinuclear localisation signal which is sufficient to target beta-globin coding sequences. The link between perinuclear mRNA localisation and translation has been investigated using cells transfected with chimeric gene constructs in which globin reporter sequences were linked to the c-myc 3'-untranslated region and the iron-responsive element from ferritin mRNA. Iron supplementation of the medium promoted translation of the chimeric mRNA as assessed by its presence in polysomes; in situ hybridisation showed that the mRNA was localised around the nucleus. Treatment with the iron chelator desferrioxamine for 16 h prevented both translation and mRNA localisation. In controls where the expressed mRNA lacked the iron-responsive element desferrioxamine had no effect upon localisation. In contrast, arrest of on-going global translation by puromycin treatment had no effect on mRNA localisation. The data suggest that if initiation of translation of a mRNA containing the c-myc localisation signal is prevented in some way then localisation does not occur, whereas once the mRNA has been localised further translation is not required to maintain mRNA localisation.

Migraine and ocular pain in "glaucoma suspect".

A relationship between glaucoma and migraine has been hypothesized by some authors, but not confirmed by others. We studied the prevalence and features of migraine and ocular pain in 460 "glaucoma suspect" patients (with ocular hypertension, but without optic disc and visual field abnormalities) and 460 controls. A higher prevalence of migraine was found in patients (13%), particularly in women (17%), than in controls (7%). At the time of the interview, migraine was still active in 68% of the patients and had decreased in the remaining 32% (prevalently those not being treated for ocular hypertension), whereas it had ceased in 52% of controls. Attacks of "ocular pain" of mild and moderate intensity were found to occur in 51% of the patients with both "glaucoma suspect" and migraine, in almost all who were not taking treatment for ocular hypertension. "Ocular pain" was time-related to the history of glaucoma. Changes in intraocular pressure may play a role in the interaction between "glaucoma suspect", migraine, and ocular pain.

Systemic lupus erythematosus and myoclonic epileptic manifestations.

Systemic lupus erythematosus (SLE) frequently involves the central nervous system (CNS) and, in fact, epileptic manifestations may be one of the earliest symptoms of SLE. These early occurrences of epilepsy, however, can easily be misdiagnosed as indication of pure epileptic syndrome when the SLE diagnosis is still largely incomplete. We present a young girl who developed myoclonic photosensitive seizures at the onset of the illness, erroneously diagnosed as manifestation of a "pure" epileptic syndrome. Shortly after the onset of an anticonvulsant therapy (lamotrigine), there was a remarkable impairment of the general clinical condition: at that time a diagnosis of SLE was made and a specific treatment began. However, the seizures persisted and evolved toward status epilepticus which needed pentobarbitone therapy in an intensive care unit (ICU). After recovery, the girl gradually got better and during the 23 months of follow-up she received only corticosteroid therapy and did not experience seizures nor SLE relapses.