Nikos Karandreas

Plasticity in human motor cortex is in part genetically determined

Neuronal plasticity refers to the ability of the brain to change in response to different experiences. Plasticity varies between people, but it is not known how much of this variability is due to differences in their genes. In humans, plasticity can be probed by a protocol termed paired associative stimulation and the changes in the motor system that are brought about by such stimulation are thought to be due to strengthening synapses which connect different neurons. We examined pairs of sisters which were either genetically identical (monozygotic) or different (dizygotic). We found that the variability within the monozygotic sister pairs was less than the variability within the dizygotic sister pairs. That plasticity in human motor cortex is in a substantial part genetically determined may be relevant for motor learning and neurorehabilitation, such as after stroke.

Large and small fiber neuropathy in chronic alcohol-dependent subjects.

Abstract  The aim of the present study was to evaluate the occurrence of large and small fiber neuropathy among alcohol‐dependent subjects and to correlate neuropathy with the pattern of alcohol abuse, age of the subjects, nutritional status, and biochemical parameters. The study sample comprised 98 consecutive alcohol‐dependent subjects without signs of malnutrition treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis. Polyneuropathy (PN) was graded using the neuropathy symptoms score and neurologic disability score, conduction velocity studies, and quantitative sensory tests. Seventy‐seven men and 21 women aged 27–70 years took part in the study. PN was diagnosed in 57 subjects (58.2%). PN of both large and small fibers was found in 25 patients (25.5%); exclusively small fiber neuropathy was observed in 12 (12.2%) and exclusively large fiber neuropathy in 20 patients (20.4%). Neuropathy was significantly correlated with the age of the subjects, duration of alcohol abuse, liver dysfunction, macrocytosis, and blood sugar levels upon admission. PN was significantly more frequent in males than in females. The two groups of exclusively large and exclusively small fiber neuropathy did not differ significantly in any clinical and laboratory parameter. Subclinical neuropathy (stage 1) was observed in 11.2%, which also did not differ significantly in any clinical and laboratory parameter from the stage 2 PN group subjects. Our findings indicate the direct toxic effect of alcohol on peripheral nerve fibers as the main etiologic factor of alcoholic PN. Long‐standing hyperglycemia may be another contributing factor. Impaired vitamin B12 utilization may be also involved.

LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) and myasthenia gravis (MG) are caused, respectively, by motor neuron degeneration and neuromuscular junction (NMJ) dysfunction. The membrane protein LRP4 is crucial in the development and function of motor neurons and NMJs and LRP4 autoantibodies have been recently detected in some MG patients. Because of the critical role in motor neuron function we searched for LRP4 antibodies in ALS patients.

Impaired interhemispheric inhibition in amyotrophic lateral sclerosis

The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unknown. Neurophysiological studies provide evidence of hyperexcitability of the motor cortex or of impairment of inhibitory intrahemispheric modulation of the corticomotoneuron in ALS. In this paper, we used TMS to elicit transcallosal inhibition of the motor cortex in ALS patients in order to investigate whether interhemispheric inhibitory mechanisms subserved by callosal fibres are also disturbed in ALS. Twenty‐five patients with ALS and 18 controls were recruited for the study. Resting Motor Threshold (RMT), Silent Period (SP) and interhemispheric inhibition (IHI) were recorded. No significant difference was detected regarding RMT or the duration of SP between patients and controls. IHI was detected in all controls. IHI was totally absent in eight patients, in another eight patients IHI did not reach a significant level and in the remaining nine patients was normal. The degree of IHI was significantly lower in ALS patients than in controls (p = 0.001). In conclusion, altered IHI in ALS patients is in line with the general pattern of reduced corticomotoneuron inhibition, being thus, one of the factors which may lead to chronic overexcitation of pyramidal cells.

Polyneuropathies in teenagers: A clinicopathological study of 45 cases

The aim of the present study was to investigate the causes of polyneuropathy in teenagers and to describe some characteristic clinical, laboratory, electrophysiological and pathological features. Forty-five patients with peripheral nervous disorders aged 13-19 were studied. Hereditary polyneuropathy of different types was diagnosed in 28 patients (62%); nine showed chronic inflammatory demyelinating polyneuropathy (CIDP) and two showed vasculitic neuropathy. In two more cases polyneuropathy was attributed to toxic agents, while among the rest, one was diagnosed as metachromatic leucodystrophy (juvenile type), one as adrenoleucodystrophy, one as porphyric neuropathy and one as Fabry disease. The high incidence of hereditary neuropathies in teenagers differs from that in adults, but is similar to that encountered in children. In our study, CIDP appears to be a frequent cause of neuropathy in teenagers, while the other causes are broadly similar to those found in studies concerning children rather than adults.

Double seronegative myasthenia gravis with anti-LRP 4 antibodies

About 10% of patients with generalized myasthenia gravis do not have detectable antibodies to acetylcholine receptor or muscle specific kinase (double seronegative myasthenia). The presence of anti-low density lipoprotein receptor-related protein 4 antibodies (LRP4 Abs) has recently been reported in variable proportion of double seronegative cases. We report the presenting characteristics of two double seronegative myasthenic patients from Greece with anti-LRP4 antibodies shortly after disease onset. The first patient, a 52-year-old male, presented with a one month history of isolated neck extensor weakness; the second patient is a 52-year-old female with three months history of ocular-bulbar-cervical myasthenic weakness. Both patients presented with mild severity and responded promptly and adequately to pyridostigmine. In the female patient thymic residual tissue was detected on CT of the mediastinum. She underwent thymectomy, and histological examination revealed follicular hyperplasia. This is the first clinical report of the presenting features of newly diagnosed myasthenia with anti-LRP4 antibodies. The clinical and therapeutic implications of the anti-LRP4 antibody positivity remain to be clarified.

Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia Gravis with thymus hyperplasia

MuSK-positive Myasthenia Gravis is in most cases clinically characterized by a progressive course with severe oculobulbar involvement or prominent neck, shoulder and respiratory muscle weakness. It is also distinguished from other forms of myastehnia through its lack of germinal centers or lymphocytic infiltrates in the thymic tissue. We present the case of a MuSK-positive female myasthenic patient with over four years slowly progressive weakness of the neck extensor muscles in the presence of thymus hyperplasia and discuss its uncommon and markedly focal clinical and electrophysiological features, as well as the excellent course under medication with pyridostigmine and prednisone, especially after thymectomy.

Repetitive Nerve Stimulation of Facial and Hypothenar Muscles: Relative Sensitivity in Different Myasthenia Gravis Subgroups

Aim: To assess the utility of repetitive nerve stimulation (RNS) in facial and hypothenar muscles in the clinical groups of myasthenia gravis (MG). Patients and Methods: We performed RNS study in the orbicularis oculi (O.O.), nasalis and abductor digiti quinti (ADQ) in 115 consecutive myasthenic patients and classified them according to the classifications of the Myasthenia Gravis Foundation of America. Patients were classified into three groups: group 1, group 2 (IIa, IIIa and IVa) and group 3 (IIb, IIIb and IVb). Results: RNS was abnormal in 95 patients (82.6%): 78.3% in the O.O., 66.1% in the nasalis and 19.1% in the ADQ. Both facial muscles were statistically more sensitive than the ADQ in all groups of patients. RNS in the O.O. was more frequently abnormal than in the nasalis only in group 1. Sensitivity to acetylcholine antibodies in myasthenic patients was 84%. Acetylcholine receptor (AChR) and muscle-specific tyrosine kinase antibodies were present in 96.7% of the patients with abnormal RNS in both facial muscles. Single-fiber electromyogram (SFEMG) was abnormal in 91.3% of the tested patients. One of the three tests used for the diagnosis of MG (AChR antibodies, SFEMG, RNS) was abnormal in 99.1% of the patients. Discussion: O.O. is the most sensitive muscle in all groups of MG followed by nasalis, while the ADQ is the muscle with the lowest sensitivity. Facial muscles, especially the O.O., should be the first to be tested in MG. The negativity of all tests (RNS, AChR antibodies, SFEMG) should question the diagnosis of MG, even in the presence of symptoms consistent with MG.

Urinary frequency in a case of Neuro-Behcet disease involving the brainstem—Clinical, electrophysiological and urodynamic features

Micturitional disturbances are reported in 5-20% of patients with Behcet disease (BD) affecting the central nervous system. However, corresponding data regarding urodynamic and electrophysiological findings are limited. A patient with known BD presented with dysarthria, diplopia and urinary frequency (36 times/day). MRI revealed an extensive lesion involving the lateral and tegmental pons, reaching the pontomedullary junction. Auditory evoked potentials indicated a left-side lesion between superior olivary nucleus and superior colliculus. Blink reflex examination indicated a location caudal to the left trigeminal root. Pudendal nerve somatosensory evoked potentials and transcranial magnetic stimulation of the perineal muscles were slightly affected. Bulbocavernosus reflex latencies were normal. EMG of the bulbocavernosus muscles showed a normal maximal voluntary contraction activity. Urodynamic studies revealed normal urine volume, maximum flow rate and residual volume. After intravenous administration of methylprednisolone diplopia and dysarthria resolved within 3 weeks. Urinary frequency remained almost unchanged for the first 8 weeks, but clearly improved during the following months. We assume that the present case of urinary frequency is the result of vasculitic lesion affecting the pontine micturition inhibitory area on the ground of Neuro-Behcet disease.

Electromyographic evidence of subclinical myopathy in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is due to a number of mutations of contractile protein genes such as β‐cardiac myosin, myosin binding protein‐C, and troponin‐T. Unlike troponin‐T, β‐myosin is a constituent of slow skeletal muscle and its mutations generally have a better prognosis. In order to investigate the usefulness of electromyography in detecting skeletal muscle involvement in HCM, 46 patients were examined using both conventional electromyography (EMG) and quantitative electromyography (QEMG) methods. The QEMG involved motor unit potential (MUP) analysis, turns/amplitude (TAA) analysis, and power spectrum analysis of the interference pattern. Using conventional EMG, myopathic findings were demonstrated in 13 patients (28%). Receiver operating characteristic (ROC) analysis of the results of a discriminant function extracted using QEMG values, identified correctly 10 out of 11 normal controls and all 9 myopathic control patients, and displayed a 15% presence of myopathy (7 patients) among the cardiomyopathy group. The duration of MUPs was the most sensitive among the quantitative parameters in differentiating normal from myopathic subjects. Since skeletal muscle involvement may be due to distinct gene mutations, normal and myopathic EMG findings may reflect HCM subpopulations with a different genetic substrate.