Extracranial venous hemodynamics in multiple sclerosis: a case-control study.

OBJECTIVES: A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria. METHODS: We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver. RESULTS: We recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999). CONCLUSIONS: With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

Multicenter external validation of the ABCD2 score in triaging TIA patients.

OBJECTIVES: A simple clinical score (ABCD(2) score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD(2) score. We aimed to prospectively validate the former score in a multicenter case series study. METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). RESULTS: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%-12%) and 16% (95% CI 10%-22%). The ABCD(2) score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57-0.88) and 90-day (c statistic 0.75, 95% CI 0.65-0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD(2) score >3 points (28%, 95% CI 18%-38%) than in patients with an ABCD(2) score < or = 3 points (4%, 95% CI 0%-9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD(2) score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04-20.84, p = 0.045). CONCLUSION: Our findings externally validate the usefulness of the ABCD(2) score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD(2) score >2.

Incidence and case fatality of subarachnoid haemorrhage in Northern Greece: the Evros Registry of Subarachnoid Haemorrhage.

BACKGROUND: Epidemiological data on subarachnoid haemorrhage incidence and case-fatality rates are scarce in the south-eastern Mediterranean region. We conducted a population-based study in Evros Province, located in north-eastern Greece, to determine subarachnoid haemorrhage incidence over a 5-year period (2001-2005). METHODS: Evros Province has a well-defined, largely homogeneous population with healthcare organised around a single tertiary-care University Hospital. We organised a prospective computerised registry of permanent Evros residents admitted or transferred to our hospital with a diagnosis of subarachnoid haemorrhage. Standard World Health Organization definitions and overlapping case-finding methods were used to identify all cases of first ever in a lifetime subarachnoid haemorrhage in all age groups, occurring during the study period. The diagnosis was confirmed by computed tomography scan in all hospitalised cases. Sudden deaths attributable to subarachnoid haemorrhage were systematically recorded province-wide by our forensic department and are included in the study. RESULTS: During the 5-year period, 51 cases of subarachnoid haemorrhage were recorded (28 men, 23 women; mean age 59+/-17 years). The crude annual incidence rates were 8.3/100,000 persons (95% confidence interval: 5.5-12.0) for men, 7.5/100,000 (4.8-11.3) for women and 7.9/100,000 (5.9-10.4) for all subjects. The standardised incidence rates for groups aged 45-84 years in the European population were 9.3/100,000 (5.8-12.8) for men, 6.5/100,000 (3.7-9.4) for women and 7.9/100,000 (5.7-10.2). The 28-day case-fatality rates for men, women and all subjects were 36% (21-54%), 35% (19-55%) and 35% (24-49%), respectively. CONCLUSIONS: The incidence and case-fatality rate of subarachnoid haemorrhage haemorrhage in Greece appear to be similar to other developed countries. No gender differences in subarachnoid haemorrhage incidence and case-fatality rate were documented.

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes.

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa=0.229, p=0.074) but was 90.2% (kappa=0.782, p<0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

Brainstem auditory evoked responses that disappear during sleep: a possible manifestation of a neurogenic vestibular evoked response.

OBJECTIVE: To present a case of unilateral hearing loss in which a brainstem auditory evoked potential (BAEP) disappeared during sleep on the symptomatic side, and to argue that this may actually be a manifestation of a neurogenic vestibular evoked potential (NVESTEP). MATERIAL AND METHOD: Brainstem auditory evoked potentials were performed in the standard manner. RESULT: A poorly organized response was obtained during wakefulness on the symptomatic side that resembled a BAEP. The BAEP for the right ear was better organized. During sleep, the response for the left ear disappeared. CONCLUSIONS: The poor organization of the response of the left ear compared to the right, and its disappearance during sleep, suggests that the response for the left ear was actually an NVESTEP and not a BAEP. The possibility of recording vestibular responses with auditory stimuli may have important implications for BAEP examinations performed during wakefulness that may lead to false negative results, in neonatal screening for hearing loss that use tone stimuli, and also in brain mapping using magnetic resonance imaging (MRI) and positron emission tomography (PET) relating to the auditory cortex.

Vestibular symptoms and signs are correlated with abnormal neurogenic vestibular evoked potentials in patients with multiple sclerosis.

OBJECTIVES: Symptoms of disequilibrium in multiple sclerosis (MS) are common. Neurogenic vestibular evoked potentials (NVsEPs) are saccular responses to tone-pip acoustic stimuli and are recordable from the parietal areas ipsilaterally to the stimulated ear. We wished to determine possible correlations of abnormal findings in NVsEP with clinical neurological findings related to the vestibular system, and demyelination seen on MRI. PATIENTS AND METHODS: NVsEPs were performed by delivering a 1 kHz tone-pip stimulus monoaurally with contralateral masking noise via headphones. Brainstem auditory evoked potentials were performed in the standard manner. RESULTS: Thirty-three patients had either been diagnosed with MS or had possible MS. There is statistical evidence that the presence of symptoms is likely to give an abnormal NVsEP, but no correlation exists between the presence or absence of vestibular symptoms and signs and an abnormal BAEP. No correlation was found between the presence of brainstem lesions on MRI and an abnormal NVsEP. Correlation exists between abnormal NVsEP and the level of disability using Expanded Disability Status Scale scores. CONCLUSION: We have found that with increasing involvement of abnormal NVsEPs, there is a significant correlation with symptoms and signs that can be referred to the vestibular system.

Neurogenic vestibular evoked potentials in three cases of vestibular system dysfunction.

OBJECTIVES: To demonstrate that neurogenic vestibular evoked potentials (NVsEP) may be specific to the vestibular system using three cases of vestibular system dysfunction and normal auditory function, METHODS: Neurogenic vestibular evoked potentials were performed by recording from the parietal areas of the scalp using a tone-pip auditory stimulus via headphones. Brainstem auditory evoked potentials (BAEPs) and NVsEP were performed in all three cases. RESULTS: Brainstem auditory evoked potentials were within normal limits in all three cases. All three patients showed abnormalities in their NVsEP In the third case, the responses normalized after treatment. CONCLUSIONS: The findings support further the hypothesis that NVsEP are specific to the vestibular system and are a separate response from the BAEP SIGNIFICANCE: Neurogenic vestibular evoked potentials is an easy examination to carry out and can be performed in any clinical neurophysiological laboratory that is familiar with BAEPs. Examinations used to diagnose vestibular system disorders at present include the glycerol dehydration test, electrocochleography, myogenic vestibular evoked potentials and electronystagmography. Neurogenic vestibular evoked potentials may also prove to be useful.

Neurogenic vestibular evoked potentials in the diagnosis of multiple sclerosis.

OBJECTIVES: To determine the value of neurogenic vesibular evoked potential (NVESTEP) studies in comparison with other paraclinical tests in demonstrating dissemination in time and space in Multiple Sclerosis (MS) and in identifying clinically silent lesions. METHOD: All patients in whom MS was suspected but the diagnosis of MS was not possible based on the McDonald criteria were included in this study. We studied 14 patients and performed visual, brainstem auditory, somatosensory and neurogenic vestibular evoked potentials in all patients, together with MRI and CSF analysis of oligoclonal bands (OB). RESULTS: Two out of the thirteen patients could be movedfrom the category of "possible MS" to "MS" using the McDonald criteria based on an abnormal NVESTEP result. CONCLUSION: Neurogenic vestibular evoked potentials are potentially useful in identifying clinically silent lesions in patients with possible MS.

Neurogenic vestibular evoked potentials using a tone pip auditory stimulus.

OBJECTIVES: To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. METHODS: Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. RESULTS: A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. CONCLUSION: Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.

Phenytoin-induced lymphocytic chemotaxis, angiogenesis and accelerated healing of decubitus ulcer in a patient with stroke.

We studied the effect of topically applied phenytoin on the healing of a decubitus ulcer in the sacral region of an immobile patient with stroke. Another similar, but smaller, ulcer was treated with conventional treatment only and served as a control. The ulcers were measured once a week and biopsies were taken from the margins before, 1 week and 2 weeks after commencing treatment with phenytoin. Clinically, phenytoin substantially accelerated the rate of healing. Microscopic examination of the biopsies showed increased lymphocytic infiltration of the phenytoin-treated lesion. Anti-CD31 immunohistochemistry revealed dense CD31+ lymphocytic infiltration and increased angiogenesis only in the phenytoin-treated lesion. Our findings suggest that phenytoin enhances wound healing by stimulating lymphocytic chemotaxis and up-regulation of angiogenesis.

Click evoked neurogenic vestibular potentials (NVESTEPs): a method of assessing the function of the vestibular system.

OBJECTIVES: To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using high intensity auditory clicks. The same stimulus is used in myogenic vestibular evoked potentials which has been shown to evoke potentials in the vestibular division of the vestibulocochlear nerve. METHODS: A whole head recording with surface EEG electrodes was performed using high intensity clicks in one normal volunteer to determine the best recording position for vestibular evoked potentials. The results were compared to responses at moderate click intensities used for brainstem auditory evoked potentials (BAEPs). The difference in the location of the two responses on the scalp was assumed to be from the vestibular system. RESULTS: Responses specific to the high intensity clicks were best obtained in the parietal areas, with no reproducible responses obtained in the same area with moderate intensity clicks normally used in BAEPs. Recordings in neurologically normal volunteers showed a consistent response with a negative polarity at around 3 ms, which we therefore called N3. Two case studies are presented. The first case is a patient with unilateral sensorineural hearing loss with NVESTEPs present, suggesting that NVESTEPs is not a cochlear response. The second case is a patient with multiple sclerosis with demyelinating lesions in the pons and an unobtainable NVESTEP response. CONCLUSION: NVESTEPs is a possible new diagnostic technique that may be specific for the vestibular pathway. It has potential use in patients with symptoms of dizziness, subclinical symptoms in multiple sclerosis, and in disorders specific for the vestibular nerve.

Bioremediation of olive oil mill wastewater: chemical alterations induced by Azotobacter vinelandii.

An environmentally friendly bioremediation system of olive oil mill wastewater (OMWW) is studied with respect to its physicochemical characteristics and degradation efficiency on major characteristic constituents. The method exploits the biochemical versatility of the dinitrogen fixing bacterium Azotobacter vinelandii (strain A) to grow in OMWW at the expense of its constituents and to transform it into an organic liquid fertilizer. The system eliminates the phytotoxic principles from OMWW and concomitantly enriches it with an agriculturally beneficial microbial consortium along with useful metabolites of the latter. The end product, branded "biofertilizer", is used as soil conditioner and liquid organic fertilizer. Growth of A. vinelandii in OMWW results in the decline of content of most of the compounds associated with phytotoxicity, and this is confirmed by the assessment of degradation yields. In parallel, during the process several other compounds noncommittally undergo degradation and biotransformation. More specifically, the biofertilization system is capable of achieving removal yields as high as 90 and 96% after 3 and 7 days of treatment, respectively. Statistical analysis of the results showed that between the periods of operation no significant difference occurs with respect to the degradation yield. Moreover, the degradation yield from 3 to 7 days of continuous operation of the system remains almost unaltered during 2 consecutive years.