A waves in electroneurography: differential diagnosis with other late responses.

Neurographic studies are an extension of clinical examination and are performed for the functional assessment of peripheral nerves. The study of motor and sensory conduction velocity and the presence, amplitude, morphology and symmetry of the response to electrical stimulation are crucial for the diagnosis and management of peripheral neuromuscular disorders. Neurography also plays an important role in the search for so-called late responses comprising the F wave, H reflex, axonal response and A wave. By analysing the parameters of each late wave, this paper addresses the pathophysiological features and the most common conditions impairing the physiology of late responses, with a special focus on A waves.

A Waves in Diabetic Neuropathy: Pathophysiology and Neurographic Images.

PURPOSE: To evaluate the presence of A waves in diabetic neuropathy, we designed a retrospective observational study recruiting patients with type II diabetes and chronic diabetic distal sensorimotor polyneuropathy. METHODS: We recruited 238 patients of both sexes aged between 41 and 89 years. Neurography was undertaken on two bilateral upper (median and ulnar) and lower (peroneal and tibial) limb nerves. As controls, we considered that neurographs performed bilaterally on the same nerves of 40 healthy subjects. RESULTS: In addition to neurographic changes typical of chronic distal sensorimotor neuropathy, patients had a 32.77% incidence of A waves, mostly found in the tibial (16.38%) and peroneal (8.8%) nerves. Among controls, A waves were found only in the tibial nerve of a single subject (2.5%). Chi-square test with Yates correction to compare the two percentages (32.77% of patients and 2.5% of healthy subjects): 13.98, P = 0.0002, highly significant. CONCLUSIONS: We postulate that demyelination may be the site of backfiring or slowing of nerve conduction velocity, explaining the appearance of A waves in their different varieties. Implementing the search for A waves in routine neurographic examination can be a useful option for the diagnosis of neuropathy and the prediction of possible latent neuropathic processes.

When the word doesn't come out: A synthetic overview of dysarthria.

Motor speech disorders are common in a number of neurological conditions including diseases involving impairment of the pyramidal, extrapyramidal, and cerebellar pathways, cranial nerves, muscular apparatus, neuromuscular plaque, and of cognitive, symbolic and mnestic activities. The diagnosis of speech disorders, namely the dysarthrias, involves the assessment of characteristic structural cerebral, prosodic, phonetic and phonemic changes, often flanked by concomitant functional, clinical, neuroradiological, neurophysiological and behavioral impairment. This paper presents a brief outline of the most significant associations to facilitate prompt differential diagnosis and thereby reduce the number of instrumental examinations required for diagnostic testing.

Video assisted trans-cervical thymectomy: a minimally invasive approach to treat non-thymomatous myasthenia gravis.

Contemporary surgical options to remove the thymus gland include median sternotomy with extended resection or minimally invasive techniques. Transcervical thymectomy has been criticized as potentially giving a "lesser" thymectomy. We describe the trans cervical approach with telescope enhancement using a standard VATS camera. This report describes the method emphasising the excellent visualization, and discuss the pro and cons over the classic trans-cervical approach or thymectomies performed by VATS or sternotomy.

Stabbing headache in patients with autoimmune disorders.

Stabbing headache is a relatively rare type of chronic "primary" headache with distinctive features with respect to more common forms of paroxysmal headache, such as cluster headache and trigeminal neuralgia. Drug treatment is empirical because of the lack of knowledge on the pathophysiology of stabbing headache. We examined 26 patients recruited over 10 years, who met the diagnostic criteria for stabbing headache. Interestingly, more than half of these patients had autoimmune disorders, including multiple sclerosis, Sjögren's disease, Systemic Lupus Erythematosus, Behçet's disease, autoimmune vasculitis, and antiphospholipid antibody syndrome. We speculate that stabbing headache may develop as a result of neuroinflammation and, at least in some cases, may be an epiphenomenon of focal demyelinating lesions of the upper or lower brain stem.

Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial.

The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy. This was a randomized, double-blind, placebo-controlled study. 61 patients with severe hepatic encephalopathy were recruited to the study. The 2 groups received either 2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and laboratory assessment, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. At the end of the study period, between the 2 groups we observed a significant difference in Everyday Memory Questionnaire -23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test 22.3 vs 0.7 (p < 0.001), Trail Making Test A -7.5 vs -2.6 (p < 0.001), Trail Making Test B -10.5 vs -3.1 (p < 0.001), Controlled Oral Word Association Test 4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time -24.5 vs -2.4 (p < 0.001), NH4⁺ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05), alanine transaminase -10.7 vs -13.6 (p < 0.001). 88% of patients treated with ALC vs 72% of patients treated with placebo showed a significant improvement in EEG. The improvement of cognitive deficits, the reduction of ammonia, and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy.

The conditioned eyeblink reflex: a potential tool for the detection of cerebellar dysfunction in multiple sclerosis.

The delayed conditioned eyeblink reflex, in which an individual learns to close the eyelid in response to a conditioned stimulus (e.g. a tone) relies entirely on the functional integrity of a cerebellar motor circuitry that involves the contingent activation of Purkinje cells by parallel and climbing fibres. Molecular changes that disrupt the function of this circuitry, in particular a loss of type-1 metabotropic glutamate receptors (mGlu1 receptors), occur in Purkinje cells of patients with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis as a result of neuroinflammation. mGlu1 receptors are required for cerebellar motor learning associated with the conditioned eyeblink reflex. We propose that the delayed paradigm of the eyeblink conditioning might be particularly valuable for the detection of subtle abnormalities of cerebellar motor learning that are clinically silent and are not associated with demyelinating lesions or axonal damage. In addition, the test might have predictive value following a clinically isolated syndrome, and might be helpful for the evaluation of the efficacy of drug treatment in multiple sclerosis.

Acetyl-L-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) represents a common complication present in well-compensated cirrhotic patients that impairs patients' daily functioning and health-related quality of life (HRQL). Acetyl-L-carnitine (ALC) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE. OBJECTIVE: This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study. Sixty-seven patients with MHE were recruited to the study. They were randomly assigned to two groups and received either 2 g acetyl-L-carnitine twice a day (n = 33) or placebo (n = 34) for 90 days. The primary efficacy measures were changes in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transpeptidase, albumin, alkaline phosphatase, prothrombin time, and ammonia. Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. RESULTS: At the end of the study period, between the two groups, we observed a significant difference in physical function (p < 0.001), role physical (p < 0.001), general health (p < 0.001), social function (p < 0.05), role emotional (p < 0.05), mental health (p < 0.05), Beck Depression Inventory (p < 0.001), TMT-B s (p < 0.001), State Trait Inventory (p < 0.001), urea (p < 0.05), NH(4)(+) (p < 0.001), and bilirubin (p < 0.001). CONCLUSIONS: This study shows that ALC treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression.

Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Fatigue is frequently reported in hepatic encephalopathy (HE) and may be related to hyperammonemia. Acetyl-L-carnitine (ALC) offers neuroprotective benefits and improves mitochondrial energetics and function. OBJECTIVE: This study evaluated the effect of exogenous ALC on physical and mental fatigue, fatigue severity, and physical activity in patients with mild and moderate hepatoencephalopathy (HE1 and HE2, respectively). DESIGN: A total of 121 patients with overt HE were recruited to the study and were subdivided into 2 groups according to their initial HE grade [HE1 (n = 61) or HE2 (n = 60)]. Thirty-one patients with HE1 and 30 with HE2 received 2 g ALC, and 30 patients with HE1 and 30 patients with HE2 received placebo twice a day for 90 d. All patients underwent clinical and laboratory assessments and automated electroencephalogram analysis. RESULTS: At the end of the study period, the ALC-treated patients in the HE1 group showed significantly better improvement than did the placebo group in mental fatigue score (-1.7 compared with -0.3; P < 0.05), the fatigue severity scale (-6.4 compared with 2.3; P < 0.001), 7-d Physical Activity Recall questionnaire score (17.1 compared with -2.5; P < 0.001), and Short Physical Performance Battery (2.1 compared with 0.2; P < 0.001); the HE2 group showed significantly better improvement in the fatigue severity scale (-8.1 compared with -5.1; P < 0.001) and 6-min walk test (19.9 compared with 2.3; P < 0.05). Significant decreases in NH(4)(+) were observed in both groups (P < 0.001). CONCLUSION: Patients with HE treated with ALC showed a decrease in the severity of both mental and physical fatigue and an increase in physical activity. This trial was registered at clinicaltrials.gov as NCT01223742.

TOT does not affect the urethral sphincter innervation: a pilot study.

INTRODUCTION AND HYPOTHESIS: To exclude a neuromuscular denervation damage due to prosthetic mini-invasive surgery using transobturator tape (TOT) by pre and postoperative electromyography (EMG) of the striated urethral sphincter. METHODS: Seventeen women with SUI were enrolled by urogynecologic and urodynamic examination. Each of them underwent EMG of striated urethral sphincter performed by 25-mm concentric needle that was put in as far as 5 mm inside internal urethral sphincter. Amplitude and duration of EMG potentials were measured during caught, maximal contraction, and at rest. Four months after TOT treatment women underwent EMG. RESULTS: The mean amplitude of EMG potentials does not show significant statistical differences between pre- and post-TOT (P=NS). The duration of potentials, instead, changed between pre and posttreatment only during the maximal contraction test (P ≤ 0.05). CONCLUSIONS: TOT prosthesis surgery, avoiding denervation and devascularization of pelvic structures does not produce damage of the urethral sphincter.

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels. AIM: The study was conducted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE. METHODS: One hundred and twenty-five patients (35 hepatitis B virus infected, 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis) were enrolled in the study. Patients were randomized either to a treatment for 60 days with Bifidobacterium and FOS (group A) or into-group receiving lactulose (group B) in double-blind. RESULTS: After 30 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B (TMT B) (P<0.005), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).After 60 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 (P<0.001), TMT A (P<0.05), TMT B (P<0.001), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001). CONCLUSION: The treatment with Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis, for its usefulness in reducing blood ammonia levels and improvement of psychometric tests.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

OBJECTIVE: Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. METHODS: Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. RESULTS: After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 mumol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow's score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00 mumol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. CONCLUSION: Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice.

A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K(+)/Cl(-) co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl(-) concentrations, which drive Cl(-) influx in response to GABA(A) receptor activation, we monitored the behavioural response to the GABA(A) receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABA(A) receptors that might contribute to the therapeutic and/or toxic effects of the drug.

Sexual dysfunction in chronic hepatitis C virus patients treated with interferon alpha and ribavirin.

The effects on sexual behavior in patients with chronic hepatitis C treated with IFN alpha plus ribavirin is an understudied field. The aim of our study was to evaluate this treatment on sexual behavior. We enrolled 170 male patients affected by chronic hepatitis C that received three MIU intramuscular leukocyte Interferon alpha plus Ribavirin thrice a week for 12 months. We assessed IFN influence by using the responses to International Index of Erectile Function (IIEF). The baseline values of each IIEF score were compared to those obtained at the end of months 1, 3, 6, and 12 as well as at the end of the follow-up period. At the end of month 1, we detected a significant reduction of IIEF scores with respect to basal values, for all administered items. These values were similar to those found at the end of month 3 for almost all parameters, being increased in only the scores of erectile function. At the end of treatment, all scores appeared reincreased, but only mean score of erectile function appeared similar to pretreatment value. The organism adapts itself in someway to the action of cytokine. Psychological influence of IFN on the patients could justify the partial impairment of sensation linked to sexual behavior. Our study provided some more information in quantification and qualification of sexual disturbances related to IFN plus Ribavirin administration in the treatment of chronic hepatitis C.

Acetyl-L-carnitine treatment in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-L: -carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90 days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90 days in group A treated with ALC, we observed a significant decrease in prothrombin time (P < 0.001), bilirubin serum levels (P < 0.01), AST (P < 0.001), fasting NH(4) serum levels (P < 0.001), Trail Making Test-A (P < 0.001) and Trail Making Test-B (P < 0.001), and a significant increase in albumin serum levels (P < 0.005), MMSE test (P < 0.001), Symbol Digit Modalities Test (P < 0.001), BDT (P < 0.001), AVL long-term test (P < 0.001) and AVL total test (P < 0.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning.

Reduced activity of cortico-striatal fibres in the R6/2 mouse model of Huntington's disease.

We have used the R6/2 mice to study cortico-striatal glutamatergic transmission by microdialysis in freely moving mice. Basal extracellular striatal glutamate concentrations were lower in R6/2 mice at 12 weeks of age, but not at 6 weeks of age, when neurological symptoms start to develop. In contrast, K-induced glutamate release was blunted in the striatum of R6/2 mice at both 6 and 12 weeks of age as compared with age-matched controls. We also found a substantial reduction in striatal pro-BDNF (brain derived neurotrophic factor) levels associated with no changes in the mature form of BDNF, as assessed by immunoblotting, in 12-week-old R6/2 mice, suggesting a reduced turnover rate of BDNF in the striatum of these mice. These data support the hypothesis of a cortico-striatal dysfunction in Huntington's disease.

Metabotropic glutamate receptors: beyond the regulation of synaptic transmission.

Metabotropic glutamate (mGlu) receptors are G-protein coupled receptors activated by glutamate, the major excitatory neurotransmitter of the CNS. A growing body of evidence suggests that the function of mGlu receptors is not restricted to the regulation of synaptic transmission. mGlu receptors are expressed in a variety of peripheral cells, including inter alia hepatocytes, pancreatic cells, osteoblasts and immune cells. Within the immunological synapses, mGlu receptors expressed by T cells might contribute to the vast array of signals generated by the antigen-presenting cells. mGlu receptors are also found in embryonic and neural stem cells. This suggests their involvement in the pathophysiology of brain tumors, which likely originates from cancer stem cells similar to neural stem cells. Ligands of mGlu3 and mGlu4 receptors are potential candidates for the experimental treatment of malignant gliomas and medulloblastomas, respectively.

Pharmacological activation of mGlu2/3 metabotropic glutamate receptors protects retinal neurons against anoxic damage in the goldfish Carassius auratus.

We examined the expression of mGlu2/3 metabotropic glutamate receptors in the retina of the goldfish Carassius auratus. mGlu2/3 receptors were expressed in all retinal layers internal to the photoreceptor layer, particularly in the outer and inner nuclear layers. Although the goldfish brain is able to tolerate prolonged periods of anoxia, we examined whether anoxia could induce retinal damage. Three hours of anoxia induced in the retina the development of apoptotic cell death, as assessed 48 h later by TUNEL staining. TUNEL-positive cells were particularly found in the inner and outer nuclear layers, and were also present in the ganglion cell layer. Pharmacological activation of mGlu2/3 receptors by systemic injection of LY379268 (0.5 mg/kg, i.p., 15 min before the onset of anoxia) substantially protected retinas against anoxia-induced cell death. In contrast, systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p., 15 min before the onset of anoxia), significantly amplified cell death. Finally, as mGlu2/3 receptors are implicated in the control of extracellular glutamate concentrations, we examined the stimulation of glutamate release in isolated goldfish retinas. Depolarizing medium containing 30 mM KCl led to a significant increase in glutamate release, which was substantially reduced by LY379268. We conclude that activation of mGlu2/3 receptors may provide a major defensive mechanism against ischemic/anoxic retinal damage.