Some New Points In Neurology

The teratogenic risk of antiepileptic drug polytherapy;

Summary Purpose: To compare the risks of fetal malformation during pregnancy associated with antiepileptic drug (AED) polytherapy and monotherapy. Methods: Statistical analysis of malformation rate and antiepileptic drug exposure data from the Australian Register of Antiepileptic Drugs in Pregnancy, and from the literature. Results: The calculated relative risk (RR) value for AED polytherapy compared with monotherapy was below 1.0 in only 3 of 14 literature publications. In the register, at 1 year postnatally there were fetal malformations in 5.32% of 282 AED polytherapy pregnancies, and in 7.84% of 791 AED monotherapy pregnancies, an RR of 0.68 [95% confidence interval (CI) 0.39-1.17). For pregnancies exposed to valproate, the RR of fetal malformation (0.39, 95% CI 0.20-0.89) was lower in polytherapy (7.26%) than in monotherapy (17.9%); the difference did not depend on valproate dosage. The RR values for fetal malformation were not significantly different for AED polytherapy and monotherapy when valproate was not involved. Logistic regression suggested that coadministration of lamotrigine may have reduced the malformation risk from valproate. Discussion: The fetal hazard of AED polytherapy relative to monotherapy may depend more on the degree of exposure to valproate than on the fact of polytherapy per se. Coadministration with lamotrigine may lower the fetal risk of valproate therapy.

Pharmacological hypotheses and therapeutic strategies for gait disorders in Parkinson’s disease;

Gait disorders form part of the axial symptoms observed in Parkinson’s disease (PD) and also represent a major source of therapeutic failure in the later stages of PD, with the appearance of freezing of gait (FOG) and falls. Double-blind clinical trials and, above all, clinical experience have demonstrated that l-DOPA is effective in reducing FOG. Dopaminergic agonists appear to be less effective than l-DOPA and lack formal proof of their efficacy. The enzyme inhibitors provide modest benefits, which need to be confirmed. Hence, these symptoms appear to be partially doparesistant and justify investigation of other major neurotransmission systems. Of the various drugs with partial noradrenergic activity, methylphenidate may improve FOG and attention disorders. Memantine has shown some value in improving motor symptoms and gait in fluctuating parkinsonian patients – possibly by reducing the effect of glutamatergic hyperactivation of the subthalamic nucleus on the pedunculopontine nucleus (PPN). The PPN’s dense cholinergic innervation also suggests that cholinesterase inhibitors may be of use, although any benefits must be set against a potential aggravation of rest tremor. The many interactions between the serotoninergic and dopaminergic systems require the implementation of clinical studies on the complex motor impact of serotoninergic treatments, which may aggravate the parkinsonian syndrome while improving gait (as is the case with paroxetine and ritanserin). This review seeks to develop the various pathophysiological hypotheses prompted by the results of fundamental studies and pilot clinical trials, with a view to justifying the implementation of confirmatory, double-blind, placebo-controlled therapeutic trials.

Objective tinnitus and essential palatal tremor in children: report of a case;

Palatal tremor is a rare neurotological disorder responsible for objective tinnitus in children. Palatal tremor may be symptomatic of an underlying neurological disease or essential when a cause cannot be identified. We report a case of an essential palatal tremor in a 10-year-old girl complaining of clicking tinnitus. No treatment was undergone as she was not obviously bothered by the ear-clicking sound. Different treatment modalities have been used for distressing tinnitus related to palatal myoclonus. Recently several publications reported satisfactory results with botulinum toxin injection, which seems to be the treatment of choice.

Favorable Influence of Subclinical Hypothyroidism on the Functional Outcomes in Stroke Patients;

Subclinical hypothyroidism (SCH) is thought to have an influence on stroke outcomes. However, few reports demonstrate a favorable relationship between the two. We evaluated this association in acute ischemic stroke. From Jan 2005 to Jun 2008, 756 acute ischemic stroke patients were recruited within seven days of onset. The patients with overt hypothyroidism/hyperthyroidism or other medical conditions that may affect thyroid function were excluded. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were measured within two days. Patients were divided into two groups: the SCH group (TSH>5.0 muU/mL and normal FT4 levels) and the control group. Stroke outcomes were assessed using two different criteria. In the first outcome model, favorable outcomes [I] were simply defined by modified Rankin Scale (mRS) scores (≤ 1), while the favorable outcomes [II] were defined as follows: a) a mRS score of 0, if the baseline National Institute of Health Stroke Scale (NIHSS) scores were<8, b) a mRS score of 0 or 1, if the NIHSS scores were 8-14, c) a mRS score 0-2, if the NIHSS scores were>14. The changes in mRS scores and the proportion of patients with favorable outcomes [I] or [II]at the 30(th) and 90(th) day were compared between the two patient groups. Of the 756 patients, 31 (4.1%) were patients with SCH. More patients from the SCH group showed improvement in NIHSS scores on the 30(th) day compared to the control group (48.4% vs. 25.3%, p=.006). In addition, the proportion of patients who exhibited favorable outcomes [I] was significantly higher in the SCH group on the 90(th) day (74.2% vs. 55.3%, p=.027) and that trend was seen as early as the 30th day (p=.102). Similarly, the proportion of the patients with favorable outcomes [II]was significantly greater in the SCH group both on the 30th (29.0% vs. 14.6%, p=.039) and 90(th) day (58.0% vs. 31.0%, p=.003). We found that acute ischemic stroke patients with SCH at admission were more likely to show favorable functional outcomes than those without SCH. We can suggest preconditioning before the stroke combined with a reduced response to stress as a possible protective mechanism.

Effectiveness of calcitonin in intermittent claudication treatment of patients with lumbar spinal stenosis: a systematic review;

STUDY DESIGN.: Systematic review. OBJECTIVE.: Analyze the level of evidence in the effectiveness of calcitonin on the treatment of neurogenic claudication in patients with lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA.: One of the most disabling features of lumbar spinal stenosis is neurogenic claudication. There have been proposed different drug therapies for it. The recommendation for calcitonin use in these patients has been sustained on autocontrolled clinical trial (Streifler et al, Neurol Neurosurg Psychiatry 1989;52:543-4), which only included 6 patients. MATERIAL AND METHOD.: We performed a search on electronic databases that included Medline and Embase; we recovered 10 original articles, of which only 4 fulfilled the RCT criteria. These articles were reviewed independent and blinded way by 6 previously capacitated reviewers to extract data and score a quality of them by the criteria of Cochrane Handbook (1996) with maximum score of 1.00 and minimum score of 0.33. RESULTS.: Score quality vary in the 4 articles: Porter and Millar, Spine 1988;13:1061-4 (score, 0.68), Eskola et al, Calcif Tissue Int 1992;50:400-3 (score, 0.88), Podichetty et al, Spine 2004;29:2343-9 (score, 0.88), and Tafazal et al, Eur Spine J 2007;16:207-12 (score, 0.92). Due to the great heterogenicity observed (sample sizes, selection criteria, doses, frequency, and duration of calcitonin, and outcome measurements), we were unable to perform a meta-analysis. Only one of these studies (Porter and Millar, Spine 1988;13:1061-4; score, 0.68) found favorable results for the use of calcitonin compared with placebo; of the 3 remaining trials none found significative evidence between drug therapy and placebo. CONCLUSION.: The present data suggest that calcitonin administration in the treatment for neurogenic claudication has no benefit in patients with lumbar spinal stenosis.