Abnormality of Contingent Negative Variation Correlates with Parkinson's Disease Severity.

Objective: We sought to assess the influence of Parkinson's disease (PD) on contingent negative variation (CNV). Patients and Methods: This prospective study included 49 patients with PD (69.7±16.5; 35 male) and 35 age- and sex-matched controls. The PD cohort was subdivided, according to the Hoehn-Yahr Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and UPDRS Part III, into 30 cases of uncomplicated PD and 19 cases of advanced PD. CNV was recorded over the frontal and central vertex with a linked bimastoid reference using a dual-stimulus paradigm with interstimulus intervals (ISIs) of 1.7 and 2.0 seconds. Results: In advanced PD, the amplitude of the late CNV over the central vertex was markedly reduced (p<0.005) at ISI of 1.7 seconds and correlated negatively with UPDRS (r=-0.32; p<0.003) and motor score (UPDRS Part III) (r=-0.45; p<0.002). Conclusion: Late CNV amplitude was significantly abnormal in PD and correlated with the severity of the motor manifestations.

Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.

OBJECTIVE: To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS). MATERIAL AND METHODS: Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies. RESULTS: Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008). CONCLUSION: High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS.

Sonography in carpal tunnel syndrome with normal nerve conduction studies.

INTRODUCTION: We assessed the yield of high-resolution ultrasonography (HRUS) in patients with clinically definite carpal tunnel syndrome (CTS) and normal nerve conduction studies (NCS). METHODS: This blinded, prospective, cross-sectional study involved 35 patients (60 hands) with clinically definite CTS and normal NCS, and 20 controls (40 hands). Cross-sectional area (CSAs) of the median nerve at the level of the pisiform bone and flexor retinaculum thickness (FRT) were measured. RESULTS: CSA was abnormal in 48.6% of patients (confidence interval 32.0-65.2%, P = 0.95). FRT was increased in only 34.3% (18.3-49.7%), but was independently abnormal in 2 patients. CSA abnormalities correlated with positive provocative tests and sensory loss. The HRUS changes were mild. CONCLUSIONS: HRUS confirms clinically diagnosed CTS in about half of the patients with normal NCS.

Single-fiber electromyography of facial and limb muscles in diabetic patients with or without neuropathy.

PURPOSE: In diabetic patients, single-fiber electromyography (SFEMG) is often abnormal in the limb muscles and is considered unreliable in diagnosis of synaptic disorders. We aimed to compare SFEMG abnormalities of frontalis muscle (FM) and extensor digitorum communis muscle in diabetic patients with neuropathy and without neuropathy. METHODS: Stimulation SFEMG of FM and extensor digitorum communis muscle was performed in matched groups of 30 diabetic patients with neuropathy and 20 diabetic patients without neuropathy. RESULTS: Single-fiber electromyography in the FM was abnormal in four diabetic patients with neuropathy and in one diabetic patient without neuropathy. Changes were rather mild. Extensor digitorum communis abnormalities were significantly more frequent-in 20 diabetic patients with neuropathy and in 7 diabetic patients without neuropathy (P < 0.001). We never observed a patient with abnormal FM but normal extensor digitorum communis muscle. CONCLUSIONS: In diabetes, FM exhibits rare and quite mild SFEMG changes. This muscle may be suitable for SFEMG in diabetic patients with clinical suspicion for synaptic disorder.

Abnormal levels of serum anti-elastin antibodies in patients with symptomatic carotid stenosis.

BACKGROUND AND OBJECTIVE: A correlation between the levels of antibodies to alpha-elastin (alpha-AEAb) and tropoelastin (tropo-AEAb) and the corresponding peptide concentration is found in human serum in health and disease. Serum elastin peptide and anti-elastin antibodies (AEAb) levels are age-related and vary with the stages of atherosclerotic vascular damage. This study aims to determine if elastin metabolism (assessed by the ratio of tropo-AEAb to alpha-AEAb) differs in patients with symptomatic carotid stenosis versus subjects with asymptomatic stenosis. PATIENTS AND METHODS: Alpha-AEAb and tropo-AEAb were measured by ELISA in blood sera of 65 patients with ultrasound verified high-grade symptomatic carotid stenosis (resulting in stroke 1-7 days before measurement) compared to 51 patients with asymptomatic stenosis. RESULTS: Serum anti-alpha-elastin IgG levels are extremely increased in symptomatic versus asymptomatic carotid stenosis. The ratio of tropo-AEAb (reflecting elastin synthesis) to alpha-AEAb (a function of elastin degradation) was 3.7 in symptomatic stenosis versus 14.2 in asymptomatic stenosis (p<0.001). CONCLUSIONS: There is a significant difference in elastin metabolism in patients with symptomatic carotid stenosis versus asymptomatic stenosis. The ratio of tropo-AEAb to alpha-AEAb as an index of elastin synthesis/degradation proves useful in investigation of atherosclerotic lesions and may represent a new immunologic marker for carotid plaque destabilization.

Hypokalemia-associated catastrophic rhabdomyolysis in ulcerative colitis.

A case of catastrophic hypokalemia-associated rhabdomyolysis in patient with ulcerative colitis (UC) is reported. A 60-year-old man presented with an exacerbation of UC and hypokalemia due to long-term diarrhea. While in the hospital, rhabdomyolysis developed in association with worsening hypokalemia. The hypokalemia was refractory to treatment and progressive course. Patient developed painful cramps of the masticatory and facial musculature associated with a moderated weakness in distal muscle groups. The weakness extended to intercostals and diaphragm muscles and led to respiratory deficiency. Serum concentration of creatine kinase was highly increased. Patient died from advancing and insurmountable cardiovascular deficiency. The causative role of hypokalemia for muscle involvement and rhabdomyolysis in patients with inflammatory bowel diseases was discussed.

Abnormalities of masseter inhibitory reflex in patients with episodic tension-type headache.

OBJECTIVE: To investigate the masseter inhibitory reflex (MIR) and its eventual changes in patients with episodic tension-type headache (TTH). METHODS: MIR was studied in 21 patients with episodic TTH and 30 healthy subjects, with age and sex matched to the study cohort. Median age of patients was 17.0 years (ranged 16~49 years), median duration of disease 12 months (1~5 years), and median frequency of headache 7.5 d per month. RESULTS: The second period of suppression (S2) of MIR was reduced in intensity and duration in 10% of controls and 66.7% (confidence interval (CI)=45.3%~85%; P<0.05) of patients with episodic TTH (chi(2)=74.9; P<0.001). In 3 (14.3%) of patients with episodic TTH, S2 was completely absent. No significant correlation between the duration of disease and headache frequency was found. CONCLUSION: Our results confirm the link between episodic TTH and reduction or absence of S2. Teenage patients with episodic TTH may exhibit marked pathological changes in S2 in contrast to older individuals.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients.

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased normal homocysteinaemia, i.e., hidden (pathologically dormant) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001). An increase of THCY with 1.0 micromol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 micromol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68%) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased ænormalÆ homocysteinaemia, i.e., æhiddenÆ (æpathologically dormantÆ) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72 percent model accuracy, p model=0.001). An increase of THCY with 1.0 æmol/L was associated with 22 percent higher risk of ischaemic stroke [adjusted OR=1.22 (95 percentCI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 æmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI percent 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63 percent, specificity>68 percent) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular cerebral isquêmico (AVCI). Todavia, em adultos jovens existe a possibilidade de aumento significativo de risco de AVCI devido a aumento "normal" da homocisteinemia, "oculta" (patologicamente adormecida) dentro de uma variação definida como normal. Neste trabalho foi investigado um modelo post-hoc de dosagem de homocisteina no plasma (HC) em pacientes jovens com AVCI agudo pareados por gênero e idade. Foi avaliado também relações entre HC e prevalência de outros fatores de risco para AVCI em 41 pacientes e 41 controles normais. MÉTODO: Foi utilizado exame clínico, procedimentos instrumentais e de neuroimagem, exame de fatores de risco, dosagem da homocisteína no plasma, outros exames laboratoriais e análise estatística. RESULTADOS: Não foram encontradas diferenças quanto a presença de fumantes, dosagem de vitaminas, creatinina sérica e perfil lipídico entre os pacientes com AVCI e os controles normais. Todavia os pacientes com AVCI apresentaram diminuição de níveis de vitamina B6 e aumento de homocisteína, fibrinogênio e trigliceridios. A análise multivariada de regressão logística mostrou diferenças significativas apenas para HC e trigliceridios independentemente associadas para fatores de risco para AVCI (72 por cento acuracia, p= 0,001). Um aumento de homocisteína de 1,0 æmol/L estava associado com aumento de 22 por cento de risco de AVCI [OR=1,22 (95 por centoIC 1,03-1,44)]. Foi evidenciado portanto um novo valor de cut-off para HC de 11,58 æmol/L em pacientes jovens com AVCI (ROC auc=0,67, 95 por cento IC 0,55-0,78, p= 0,009). CONCLUSÃO: Este novo valor de cut-offpara a homocisteína discrimina claramente a ausência ou presença de AVCI (sensibilidade >63 por cento, especificidade >68 por cento) independente do gênero ou idade e deve ser aplicado para uma melhor avaliação precoce de pacientes jovens com risco de AVCI.

Stimulated jitter in the masseter muscle: normative values.

Nineteen healthy volunteers (median age, 25; range, 18-51 years) were enrolled in a study to obtain normative values for stimulated jitter in the masseter muscle. Axonal microstimulation was performed via a monopolar needle electrode introduced in the masseter 2-2.5 cm above the mandibular angle on the line connecting it with the lateral canthus. The recording single-fiber electromyography (SFEMG) electrode was inserted anteriorly in the twitching area of the muscle. The mean consecutive difference (MCD) values for the 426 endplates studied followed a distribution skewed to the left, with a minimum value of 4.3 micros, maximal 44.7 micros, and a maximum of distribution at 11 micros. Mean pooled MCD measured 16.0 micros, and the mean of mean MCD per study was 13.6 micros. The value of the 95th upper percentile for an individual fiber was 29.3 micros. We suggest an upper normal limit for mean MCD per study of 21 micros and upper normal limit of MCD for individual fibers of 30 micros. The stimulated jitter study of masseter muscle is easy and reliable.

Abnormal levels of serum antielastin antibodies in children with diabetes mellitus type 1.

Antibodies to alpha-elastin (elastin breakdown product) and elastin sequences devoid of cross-linked regions (linear elastin) are found in the serum of all human subjects and correlate with their respective serum peptide levels. The aim of this study was to determine if the serum level of antielastin antibodies (AEAbs) differs between type 1 diabetic children and nondiabetic children. Enzyme-linked immunosorbent assay was used to measure the levels of immunoglobulin (Ig)G and IgM AEAbs in the sera of 45 diabetic children (mean age 12.8 +/- 3.2 years, diabetes duration 5.3 +/- 3.6 years). Twenty-two children presented with vascular complications (group 1), whereas 23 displayed no vascular complications (group 2). The controls were 18 healthy children (mean age 11.9 +/- 2.3 years). Diabetic patients showed statistically significant higher levels of IgM alpha-AEAbs (0.82 +/- 0.26 vs 0.61 +/- 0.14, p = .0013) than the control group. In group 1, alpha-AEAbs showed statistically significant higher level than controls: IgG (0.86 +/- 0.42 vs 0.59 +/- 0.12; p = .0109) and IgM (0.88 +/- 0.24 vs 0.61 +/- 0.14; p = .0001). IgM antilinear elastin antibodies (ALEAbs) in group 1 were significantly lower than in controls (0.462 +/- 0.191 vs 0.652 +/- 0.127; p = .0009). IgG alpha-AEAbs showed correlation with microalbuminuria (r = -.26; p = .05) and IgM ALEAbs correlated with microalbuminuria (r = -.32; p = .035). IgG alpha-AEAbs correlated with neuropathy (r = -.32; p = .035). Group 1 patients displayed a correlation between IgG ALEAbs and retinopathy (r = -.48; p = .023) and IgM ALEAbs and microalbuminuria (r = .52; p = .014). Levels of AEAbs and ALEAbs can serve as immunologic markers of the extent of elastin degradation. These markers may provide a tool to study elastin metabolism and a potential clinical role for AEAbs in the pathogenesis and development of vascular complications in diabetic children.

False localising levels in spinal cord compression.

OBJECTIVE: To describe three cases with false localising levels illustrating the difficulty in clinical diagnosis of spinal cord compression. PATIENTS AND METHODS: Three patients (aged 53, 55 and 57 years) developed acute (in one) and subacute (in two) spinal cord syndrome with paraparesis, bladder symptoms and sensory levels suggesting lower thoracic or higher lumbar involvement. Imaging at suspected levels was normal. Follow-up investigations after a significant delay showed compression at higher levels (up to 11 segments). Diagnoses were surgically verified. In one patient who died, post mortem investigation discloseed a caudally situated artery of Adamkiewicz and absent vicarious vessels at T7-T8 that are usually present in such cases. CONCLUSIONS: The well known but rare phenomenon of false localizing sensory levels in spinal cord syndromes should be kept in mind. Its causes can lie in remote higher levels of compressive lesion or in vascular compromise due to variants of the blood supply.

Predictive value of median-SSEP in early phase of stroke: a comparison in supratentorial infarction and hemorrhage.

OBJECTIVE: To compare the prognostic value of median somatosensory evoked potentials (M-SSEP) changes in the early phase of supratentorial infarction and hemorrhage. MATERIAL AND METHODS: This study includes 130 patients (mean age 62+/-11.4 years, 43 women, large middle cerebral artery territory infarction in 36 patients, restricted/lacunar in 55, massive supratentorial hemorrhage in 10, small/medium size hemorrhage in 31). M-SSEP were recorded early (0-7 days in ischemia, 0-21 days in hemorrhage) and patients stratified into groups with absent, abnormal, normal response. Clinical state was determined by the Medical Research Council (MRC) scale, Barthel Index and Rankin score and followed for at least 6 months. RESULTS: Moderate prognostic correlation was established between N20-P25 amplitudes (r=0.34, p<0.05) and N20-P25 amplitude ratio (r=0.45, p<0.01) and Barthel Index at 6 months in patients with ischemic stroke. Moderate relationship (r=-0.34, p<0.05) exists also between N20-P25 ratio and Rankin score at 6 months in patients with small/medium size hemorrhage. In large infarctions and small/medium size cerebral hemorrhages correlations with all clinical indices of outcome are weak. In massive hemorrhage, only a weak correlation (r=-0.19, p<0.05) between amplitude ratio and Rankin score was found. The combination of initial MRC and N20-P25 amplitude ratio has 10% (in hemorrhage) to 15% (in infarction) greater prognostic value (p<0.05) than initial alone. CONCLUSIONS: M-SSEP have independent predictive value regarding functional recovery in ischemic stroke and small/medium size cerebral hemorrhage. Combined assessment of initial MRC and M-SSEP substantially improves prognosis in acute stroke.

Muscle hypertrophy with complex repetitive discharges in C-6 radiculopathy.

OBJECTIVE: To report on a case of post-denervation muscle hypertrophy in an unusual distribution. CASE REPORT: A 52-year-old patient with severe flaccid paraparesis after polio developed unilateral C-6 radiculopathy that resolved with conservative treatment. Within 2 years marked hypertrophy, stiffness and pain in the muscles in the affected myotome developed. EMG discovered abundant complex repetitive discharges (CRD) within hypertrophic muscles. On biopsy, true hypertrophy of muscle fibers and some group atrophy was found. Steroid treatment relieved the symptoms and significantly suppressed the CRD. The possible causative role of CRD for hypertrophy in partially denervated muscle is discussed.

Prognostic value of median and tibial somatosensory evoked potentials in acute stroke.

The predictive values of early somatosensory evoked potentials (SSEPs) for the functional outcome after stroke are investigated. Ninety-four stroke patients (mean age: 61.2, S.D.: 11.8) with CT confirmed diagnoses of middle cerebral artery (MCA) infarction in 71 and supratentorial intracerebral hemorrhage in 23. Median and tibial SSEPs were recorded within 3 days of onset. SSEP parameters were compared to motor (MRC) and functional ability (Barthel index) followed up at 1, 3, 6 and 12 months. Upper limb MRC remains the strongest single predictor of functional outcome, determining 54.3% of Barthel index value at 12 months. The highest predictive value among SSEP parameters has N20-P25 amplitude ratio-34.5%. Combined application of upper limb MRC and N20-P25 amplitude ratio provided significantly stronger prognostic information-66%. Combined assessment of SSEP parameters and muscle power in acute stroke considerably improves prediction of functional outcome.

The bifid visual evoked potential-normal variant or a sign of demyelination?

OBJECTIVE: To prospectively evaluate the diagnostic significance of bifid VEP at initial presentation. MATERIALS AND METHODS: A hundred and sixteen patients (46 males and 70 females, age 15-54, mean 28.8), with a clinical suspicion of multiple sclerosis (MS), underwent pattern-shift VEP investigation between 1992 and 1998. They were further followed by clinical, CSF, MRI means for at least 5 years (mean 7.2). Twenty-six patients remained healthy, while 90 developed demyelinating disease (in 71 MS and in 19 optic neuritis was the final diagnosis). Fifty healthy persons (20 males aged 18-51, mean 28.8 and 30 females aged 18-48, mean 26.2) represented the control group. The number of persons with bifid VEP in each group are analyzed. RESULTS: In the controls one out of 50 exhibited bifid VEP configuration. Of 26 patients with unconfirmed suspicion for MS again one had such responses. Bifid VEP were significantly more frequent in patients with demyelinative pathology (nine out of 90, 10.0%, P (chi-squared) < 0.01). CONCLUSIONS: Bifid VEP is rarely observed in healthy persons. Its presence should suggest the possibility of demyelinating disease and prompt further investigation and follow-up.

Can SSEP results predict functional recovery of stroke patients within the "therapeutic window"?

OBJECTIVES: To investigate the prognostic value of median somatosensory evoked potentials (mSSEP) within the "therapeutic window" of ischemic stroke. MATERIALS AND METHODS: Twenty-two patients (mean age 60.8 +/- 14.8 years) with first ischemic stroke in middle cerebral artery territory without contraindications for thrombolysis underwent mSSEP investigation within 3 hours of onset. Stroke topography was verified within 48 hours by computed tomography. M-SSEP results (presence, amplitude and amplitude ratio, latency and central conduction time) were compared to severity of motor deficit at onset and to recovery at 6 months. RESULTS: M-SSEP were present in 17 patients, 7 of whom had partial and 10--complete motor recovery. Absence of mSSEP was found in 5 persons. None recovered function of the arm and only 2 were ambulatory at 6 months. CONCLUSIONS: In the earliest phase of ischemic stroke absence of mSSEP response is reliable predictor of poor functional outcome.

Median SSEP changes in hemiplegic stroke: long-term predictive values regarding ADL recovery.

OBJECTIVE: To assess the predictive value of median somatosensory evoked potentials (SSEP) in the acute phase of brain infarction or hemorrhage regarding long-term prognosis. MATERIALS AND METHODS: Ninety-four stroke patients mean age 61.2, SD 11.8) were included. CT confirmed diagnoses were: cortical middle cerebral artery (MCA) infarction in 35; subcortical MCA 11; mixed 25. By size, infarctions were: massive, 29; restricted, 33; and lacunar, 9. The number of patients with thalamic hemorrhage was 8; putamenal hemorrhage, 7; other, 8. All patients presented with severe hemiparesis (54) or hemiplegia (40) with hemihipoesthesia in 89 patients. Median SSEP were recorded early (up to 7th day, mean 5.2 days, SD 0.72). SSEP parameters (presence/absence of SSEP, absolute and relative latency, amplitude of early waveforms) were compared to motor (Medical Research Council scale) and functional ability (Barthel index) at 3 and 12 months after stroke. RESULTS: Absolute N20 amplitudes and amplitude ratio evidenced almost similar predictive values that reached 66.4% at 12 months. Combined application of N20 and MRC gains provided significantly stronger prognostic information which reached 72%. CONCLUSIONS: Median SSEP parameters may serve as independent predictors of outcome. Most informative in prognosis in the early stage of stroke was the combined assessment of MRC and N20-P25 amplitude ratio.