Nikolaos Karandreas

Validation of the ABCD Score in Identifying Individuals at High Early Risk of Stroke After a Transient Ischemic Attack. A Hospital-Based Case Series Study

Background and Purpose— A simple score derived in the Oxfordshire Community Stroke Project (ABCD score) was able to identify individuals at high early risk of stroke after a transient ischemic attack (TIA) both in a population-based and a hospital-referred clinic cohort. We aimed to further validate the former score in a cohort of hospitalized TIA patients. Methods— We retrospectively reviewed the emergency room and hospital records of consecutive patients hospitalized in our neurological department with a definite TIA according to the World Health Organization (WHO) criteria during a 5-year period. The 6-point ABCD score (age [<60 years=0, ≥60 years=1]; blood pressure [systolic ≤140 mm Hg and diastolic ≤90 mm Hg=0, systolic >140 mm Hg and/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 to 59 minutes=1, ≥60 minutes=2]) was used to stratify the 30-day stroke risk. Results— The 30-day risk of stroke in the present case series (n=226) was 9.7% (95% CI, 5.8% to 13.6%). The ABCD score was highly predictive of 30-day risk of stroke (ABCD=0 to 2: 0%, ABCD=3: 3.5% [95% CI, 0% to 8.2%], ABCD=4: 7.6% [95% CI, 1.2% to 14.0%], ABCD=5: 21.3% [95% CI, 10.4% to 33.0%], ABCD=6: 31.3% [95% CI, 8.6% to 54.0%]; log-rank test=23.09; df=6; P=0.0008; P for linear trend across the ABCD score levels <0.00001). After adjustment for stroke risk factors, history of previous TIA, medication use before the index TIA, and secondary prevention treatment strategies, an ABCD score of 5 to 6 was independently (P<0.001) associated with an 8-fold greater 30-day risk of stroke (hazard ratio, 8.01; 95% CI, 3.21 to 19.98). Conclusions— Our findings validate the predictive value of the ABCD score in identifying hospitalized TIA patients with a high risk of early stroke and provide further evidence for its potential applicability in clinical practice.

Rituximab therapy in monoclonal IgM-related neuropathies

Monoclonal IgM-related neuropathies constitute a heterogeneous group of disorders, which are generally poorly responsive to treatment. Rituximab, a chimeric monoclonal antibody against the CD20 molecule, has been used with success in patients with neuropathy and monoclonal IgM with anti-MAG or anti-GM1 ganglioside activity. Based on this observation, four patients were treated with IgM-related neuropathy with rituximab. Between January 1999 – December 2000, four patients with IgM-related neuropathy (one with chronic inflammatory demyelinating polyneuropathy (CIDP) and three with sensorimotor demyelinating neuropathy) were treated with rituximab. Rituximab was administered at a standard dose of 375 mg m−2 iv weekly for a consecutive 4 weeks; 3 months later, four additional weekly courses were administered to patients who did not experience deterioration of their neuropathy symptoms. Neurological evaluation was performed before each rituximab infusion and at 1 week and 2 months after last infusion and every 6 months the following years; including motor (MRC in six muscle groups, 9-hole peg test, 10 m walk, hand grip strength), sensory neuropathy (vibration threshold and sensory subjective score) assessment. Neurophysiological parameters were also assessed (MNCV, SNCV, CMAP, SNAP). Strength improved in three of four patients; including the patient with CIDP. This patient developed a significant worsening of her weakness 3 weeks after the initiation of rituximab. This phenomenon coincided with a serum monoclonal IgM flare and resolved spontaneously 1 week later. Her improvement is ongoing for more than 5 years. Considering neurophysiological parameters, two patients showed a slight improved regarding conduction velocities and CMAP (10%) and the patient with IgM flare had a transient worsening of conduction velocities followed by improvement. In conclusion, rituximab is a safe and well-tolerated treatment which may be effective in some patients with IgM-related neuropathy.

Validation of the Dutch Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain

The Douleur Neuropathique 4 questionnaire (DN4) was developed by the French Neuropathic Pain Group and is a simple and objective tool, primarily designed to screen for neuropathic pain. The aim of our study is to validate the DN4 in the Greek language.

Polyneuropathy induced by HIV disease and antiretroviral therapy

OBJECTIVE To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. METHODS We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. RESULTS Severity of the disease (CD4 +count) correlated to conduction velocities of peroneal (p < 0.01, Spearmans rank correlation), sural (p < 0.01) and median nerves (p < 0.05/p < 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p > 0.3) but correlated to reduced IENFD in the ankle (r = -0.24, p < 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 +count. CONCLUSIONS Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. SIGNIFICANCE These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.

Carpal Tunnel Syndrome: Associations between Risk Factors and Laterality

Aims: The investigation of the association between known risk factors and laterality in patients with carpal tunnel syndrome (CTS). Patients and Methods: 130 consecutive subjects with CTS only, or mainly, in the left hand were compared with 130 consecutive subjects with CTS only, or mainly, in the right hand. The following parameters were recorded: age, sex, job, handedness, hand mainly used in daily activities, BMI, diabetes mellitus, thyroid dysfunction, wrist trauma and connective tissue diseases. Results: A left dominant hand was independently associated with 13-fold higher odds for left-hand CTS, while a right dominant hand had 5-fold higher odds for right-hand CTS. Right-hand CTS was more frequent in younger subjects and females. Conclusion: Older age, higher BMI and diabetes mellitus were more prevalent in patients with bilateral CTS. Age and BMI were independently associated with bilateral CTS.

Oxaliplatin-Induced Neuropathy: A Long-Term Clinical and Neurophysiologic Follow-Up Study

BACKGROUND Oxaliplatin is an effective drug used mainly for advanced colorectal cancer. Neurotoxicity is the major side effect of oxaliplatin. The present clinical and neurophysiologic study was conducted to evaluate patients receiving oxaliplatin therapy. PATIENTS AND METHODS Thirty-one consecutive patients with colorectal cancer who received oxaliplatin therapy were followed up for more than 3 years. The patients underwent clinical and neurophysiologic tests for large and small fiber function at every visit. RESULTS Most of the patients received oxaliplatin-based chemotherapy at the initial dose of 130 mg/m(2) for 6 to 8 cycles, normally every 3 weeks. Acute neurotoxicity with cold and mechanical hyperalgesia was reported by the vast majority of patients after each cycle of therapy and was confirmed by the quantitative sensory, filament, and axon reflex test. Chronic sensory cumulative neuropathy developed in most of the patients after the middle of therapy with numbness and was assessed using clinical scales, nerve conduction studies, and the vibration threshold. Our results support the persistence of the sensory nerve deficits for years after cessation of oxaliplatin therapy. CONCLUSION Our study has confirmed the results of a few previous long-term studies concerning the persistence of chronic large sensory fiber neuropathy and the influence of the cumulative dose of oxaliplatin on the development and severity of the chronic neuropathy. Our findings have improved the knowledge about the acute oxaliplatin-induced neurotoxicity using the C-fiber axon reflex response.

Differential sensitivity of thick and thin fibers to HIV and therapy-induced neuropathy

The study assessed HIV-related and anti-retroviral therapy-induced neuropathy in myelinated and unmyelinated nerve fibers. One hundred consecutive HIV patients were examined clinically and standard nerve conduction velocities were measured. In addition, electrically induced sympathetic skin response (SSR) was assessed in the palms and soles. The difference in delay of SSR in palms and soles (DeltaSSR) was calculated as an indirect measure of C-fiber conduction velocity. Thick fiber conduction velocities significantly decreased with age and increasing stage of the disease, whereas no effect of stage was found for DeltaSSR (p=0.6). In contrast, medication of at least one of the most known neurotoxic drugs zalcitabine, stavudine, or didanosine did not result in significantly lower conduction velocities in thick fibers (51.29+/-3.4 m/s vs. 50.86+/-3.5 m/s), but was related to an increased DeltaSSR. DeltaSSR allows an indirect measurement of C-fiber conduction velocity. In HIV this measure of unmyelinated sympathetic fibers was most sensitive to anti-viral treatment whereas conduction velocity of myelinated somatic fibers was more sensitive to disease-related neuropathy. The results suggest that HIV neuropathy preferably affects myelinated and anti-retroviral therapy unmyelinated fibers.

Muscle Fiber Conduction Velocity, Muscle Fiber Composition, and Power Performance

PURPOSE The aim of this study was to explore the relationship between muscle fiber conduction velocity (MFCV), fiber type composition, and power performance in participants with different training background. METHODS Thirty-eight young males with different training background participated: sedentary (n = 10), endurance runners (n = 9), power trained (n = 10), and strength trained (n = 9). They performed maximal countermovement jumps (CMJ) and maximal isometric leg press for the measurement of the rate of force development (RFD). Resting vastus lateralis MFCV was measured with intramuscular microelectrodes on a different occasion, whereas muscle fiber type and cross-sectional area (CSA) of vastus lateralis were evaluated through muscle biopsies 1wk later. RESULTS MFCV, CMJ power, RFD, and % CSA of type II and type IIx fibers were higher for the power-trained group (P < 0.001). No difference was found between sedentary participants and endurance runners in these variables, but both of these groups performed worse than strength/power participants. Close correlations were found between MFCV and fiber CSA as well as the % CSA of all fiber types as well as with RFD and CMJ power (r = 0.712-0.943, P < 0.005). Partial correlations revealed that the % CSA of IIx fibers dictates a large part of the correlation between MFCV and RFD, power performance. Significant models for the prediction of the % CSA of type IIa and type II as well as the CSA of all muscle fibers based upon MFCV, RFD, and CMJ were revealed (P = 0.000). CONCLUSION MFCV is closely associated with muscle fiber % CSA. RFD and jumping power are associated with the propagation of the action potentials along the muscle fibers. This link is regulated by the size and the distribution of type II, and especially type IIx muscle fibers.

Motor and sensory polyneuritis with distal conduction failure as uncommon complication of an acute Rickettsia conorii infection

Rickettsia conorii is endemic in the Mediterranean region. Infections are mostly benign and neurological involvement is unusual. We describe a case of a man who presented with acute facial nerve palsy followed by flaccid tetraparesis due to an electrophysiologically established polyneuritis with distal conduction failure. Elevated IgM antibody titres for R. conorii were documented by indirect immunofluorescent antibody test. After doxycycline therapy, the patient presented a rapid clinical improvement. Repeated electrophysiological examinations revealed significantly restored compound muscles, and sensory action potentials, corresponding to the clinical course after treatment and ex juvantibus, indicate the causative relation between R. conorii infection and the described clinical syndrome.

Rapid Screening for Carpal Tunnel Syndrome: A Novel Method and Comparison With Established Others.

Purpose: The authors have observed that in healthy people, the Ulnar wrist-to-first dorsal interosseous distal motor latency does not differ significantly compared with median wrist-to-abductor pollicis brevis distal motor latency. The aim of our study was to investigate whether the difference between these two latencies can be used as a screening tool for diagnosing carpal tunnel syndrome and how this technique compares with other established techniques. Methods: The study was set up as a prospective observational study. As gold standard for the clinical diagnosis of carpal tunnel syndrome, the authors used the opinion of two neurologists who independently examined the patients. A third neurologist, also independently, performed the electrophysiological study. Results: Eighty-four subjects, 42 patients and 42 age- and sex-matched controls, participated in the study. Among all subjects using a receiver operating characteristic curve analysis, the area under the curve was 0.924 (95% CI, 0.857–0.991; SE, 0.034; P < 0.001). To detect carpal tunnel syndrome, at a cutoff score of equal to or greater than 0.575 milliseconds, our technique showed a sensitivity of 91%, a specificity of 93%, a positive predictive value of 93%, and a negative predictive value of 91%. Compared with other “classical” techniques, our technique showed better area under the receiver operating characteristic curve and better Youden index. Conclusions: The median wrist-to-abductor pollicis brevis motor latency minus ulnar wrist-to-first dorsal interosseous motor latency may be used as a novel rapid screening tool of patients suffering from carpal tunnel syndrome.