Monica Storti

Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

Resting motor threshold in idiopathic generalized epilepsies: A systematic review with meta-analysis

Resting motor threshold (rMT) assessed by means of Transcranial Magnetic Stimulation (TMS) is thought to reflect trans-synaptic excitability of cortico-spinal neurons. TMS studies reporting rMT in idiopathic generalized epilepsies (IGEs) yielded discrepant results, so that it is difficult to draw a definitive conclusion on cortico-spinal excitability in IGEs by simple summation of previous results regarding this measure. Our purpose was to carry out a systematic review and a meta-analysis of studies evaluating rMT values obtained during single-pulse TMS in patients with IGEs. Controlled studies measuring rMT by single-pulse TMS in drug-naive patients older than 12 years affected by IGEs were systematically reviewed. rMT values were assessed calculating mean difference and odds ratio with 95% confidence intervals (CI). Fourteen trials (265 epileptic patients and 424 controls) were included. Patients with juvenile myoclonic epilepsy (JME) have a statistically significant lower rMT compared with controls (mean difference: -6.78; 95% CI -10.55 to -3.00); when considering all subtypes of IGEs and IGEs other than JME no statistically significant differences were found. Overall considered, the results are indicative of a cortico-spinal hyper-excitability in JME, providing not enough evidence for motor hyper-excitability in other subtypes of IGE. The considerable variability across studies probably reflects the presence of relevant clinical and methodological heterogeneity, and higher temporal variability among rMT measurements over time, related to unstable cortical excitability in these patients.

The diagnostic value of urinary incontinence in the differential diagnosis of seizures.

PURPOSE Urinary incontinence may occur both in epileptic seizures (ES) and in non-epileptic events (NEE) such as psychogenic nonepileptic events (PNEEs) and syncope. A comprehensive search of the literature to determine the accuracy of this physical finding and its prevalence in epileptic seizures and syncope is still lacking. To undertake a systematic review to determine sensitivity, specificity and likelihood ratios (LR) of urinary incontinence in the differential diagnosis between ES and NEEs (including syncope and PNEEs). METHODS Studies evaluating the presence of urinary incontinence in ES and NEEs were systematically searched. Sensitivity, specificity, positive and negative likelihood ratio (pLR, nLR) of incontinence were determined for each study and for the pooled results. RESULTS Five studies (221 epilepsy patients and 252 subjects with NEEs) were included. Pooled accuracy measures of urinary incontinence (ES versus NEEs) were: sensitivity 38%, specificity 57%, pLR 0.879 (95% CI 0.705-1.095) and nLR 1.092 (95% CI 0.941-1.268). For each comparison (epileptic seizures versus NEEs; ES versus syncope; ES versus PNEEs), pooled accuracy measures for urinary incontinence showed a statistically not significant pLR (the 95% CI of the pooled value included 1, and the LR value of 1 has no discriminatory value). CONCLUSIONS A pooled analysis of data from the literature shows that urinary incontinence has no value either in the differential diagnostic between ES and syncope/PNEEs. Systematic reviews with pooled analyses of data from the literature allow an increase in statistical power and an improvement in precision, representing a useful tool to determine the accuracy of a certain physical finding in the differential diagnosis between ES and other paroxysmal events.

Focal nonconvulsive seizures during detoxification for benzodiazepine abuse

Chronic benzodiazepine (BDZ) abuse is currently treated with detoxification using a low-dose flumazenil infusion, a relatively recently developed and promising procedure. Given the possibility reported in the literature of the occurrence of generalized seizures during therapeutic BDZ detoxification, we usually administer preventive antiepileptic drug (AED) therapy. We describe two patients with no previous history of seizures or evidence of intracerebral lesions who, during detoxification for benzodiazepine abuse, developed repetitive focal nonconvulsive seizures instead of generalized seizures, even with appropriate doses of preventive AED therapy. There are no previous reported cases of focal nonconvulsive seizures occurring during this procedure or, more generally, during abrupt BDZ discontinuation. The cases we describe suggest that during detoxification for BDZ abuse, not only generalized, but also focal nonconvulsive seizures may occur. In this context, the focal seizures probably result from a diffuse decrease in the seizure threshold (caused by a generalized excitatory rebound), which may trigger focal seizures arising from cortical regions with higher intrinsic epileptogenicity. Detoxification for benzodiazepine abuse, even if performed with adequate-dosage AED treatment, may not be as safe a procedure as previously considered, because not only convulsive, but also nonconvulsive seizures may occur and go unnoticed. It is therefore strongly advisable to perform this detoxification under close medical supervision and to maintain a low threshold for EEG monitoring in the event of sudden onset of behavioral changes.

Spinal cord involvement in patients with cirrhosis.

A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases; this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt. Hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while sensory and sphincter disturbances have rarely been described and are usually less important. The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis. Magnetic resonance imaging is often unremarkable; however, also intracerebral corticospinal tract abnormalities have been reported recently. The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest. HM responds poorly to blood ammonia-lowering and other conservative medical therapy. Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades. Other surgical treatment options in HM include surgical ligation, shunt reduction, or occlusion by interventional procedures.

Infliximab-related seizures: a first case study

Seizures following infliximab treatment are very rare and, to date, there is no detailed description of EEG abnormalities with cerebral radiological findings reported in cases with infliximab-related seizures. We describe a patient who acutely developed seizures temporally related to infliximab treatment, which disappeared after drug withdrawal. MRI showed encephalopathy involving mainly cortical regions and EEGs showed focal paroxysmal activity which completely disappeared a few days after infliximab withdrawal. No other plausible cause of the seizures was identified. The clear temporal association between seizure onset and infliximab treatment as well as the clinical improvement and disappearance of focal epileptiform activity after drug withdrawal indicated an evident correlation between seizures and infliximab therapy. The coexistence of pathological findings on MRI suggested that seizures were secondary to the encephalopathy. Further studies are required to evaluate whether infliximab per se has an epileptogenic effect or whether the seizures are caused by encephalopathy involving cortico-subcortical regions.

Transitory stapedial myoclonus in a patient with benign fasciculation syndrome.

OBJECTIVE We report a previously undescribed association between transitory stapedial myoclonus, objective tinnitus and benign fasciculation syndrome. METHOD Case report and review of the world literature regarding stapedial myoclonus. RESULTS A 30-year-old man with a diagnosis of benign fasciculation syndrome abruptly developed severe, low-pitched tinnitus on the right side. Otoscopic examination revealed rhythmic movement of the tympanic membrane, which was synchronous with the tinnitus. No palatal spasm was noted on nasopharyngeal examination. Brain magnetic resonance imaging and pure tone audiometry were unremarkable. Based on these findings, a diagnosis of objective tinnitus due to stapedial myoclonus was made. The objective tinnitus spontaneously disappeared within 48 hours of its appearance, but in the following days the patient suffered frequent, brief episodes of objective tinnitus lasting only a few seconds. CONCLUSION The occurrence of stapedial myoclonus in this patient indicated the presence of an underlying motor unit hyper-excitability. This case suggests that, in some patients, stapedial myoclonus may represent the clinical expression of diffuse motor unit hyper-excitability.

Homocysteine-lowering interventions are ineffective in preventing myocardial infarction.

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Vitamin E is ineffective in preventing stroke

Stroke is a leading cause of death and long-term disability worldwide. Vitamin E (tocopherol) is an antioxidant which may protect against atherogenesis by acting as a scavenger of free radicals with subsequent reduced oxidation of low-density lipoprotein cholesterol and several other favourable effects on plaque stability, platelet aggregation and tendency to thrombosis. However, a recent meta-analysis of 13 randomised controlled trials (166 282 participants) showed that, compared with placebo, vitamin E supplementation does not significantly prevent stroke of any type (RR 1.01; 95% CI 0.96 to 1.07).1 The statistical question addressed by this meta-analysis was whether or not vitamin E …

ECG myogenic artifacts during clonic seizures: a disturbing (and interesting) finding

During motor seizures myogenic artifacts may appear on ECG. We report a patient with recurring convulsive seizures involving left side of his body in whom ECG served as a surrogate of electromyography (EMG), showing myogenic artifacts strongly correlated with clonic jerks. The possibility of standard ECG of recording myogenic potentials when clonic seizures occur is something intriguing, being at the same time both disturbing and informative. In such cases standard ECG works as an EMG, although ECG filter, sensitivity and paper speed is different from EMG currently used in neurophysiological laboratory. However, using standard ECG acquisition parameters, muscular activity may be recorded without excessive attenuation of high-frequency myogenic potentials, permitting to indicate the frequency of clonic movements. On the other hand, whenever possible, positioning of ECG surface electrodes on limbs not (or less) involved in clonic epileptic movements may permit to obtain a sufficiently informative ECG recording with less amount of myogenic artifacts, thus providing essential information on heart rate and rhythm.