Archives of neurology最新文献

Background: Cutaneous autonomic function can be quantified by the assessment of sudomotor and vasomotor responses. Although piloerector muscles are innervated by the sympathetic nervous system, there are at present no methods to quantify pilomotor function.

Objective: To quantify piloerection using phenylephrine hydrochloride in humans.

Design: Pilot study.

Setting: Hospital-based study.

Participants: Twenty-two healthy volunteers (18 males,4 females) aged 24 to 48 years participated in 6 studies.

Interventions: Piloerection was stimulated by iontophoresis of 1% phenylephrine. Silicone impressions of piloerection were quantified by number and area. The direct and indirect responses to phenylephrine iontophoresis were compared on both forearms after pre treatment to topical and subcutaneous lidocaine and iontophoresis of normal saline.

Results: Iontophoresis of phenylephrine induced piloerection in both the direct and axon reflex–mediated regions, with similar responses in both arms. Topical lidocaine blocked axon reflex–mediated piloerection post-iontophoresis (mean [SD], 66.6 [19.2] for control impressions vs 7.2 [4.3] for lidocaine impressions;P.001). Subcutaneous lidocaine completely blocked piloerection.The area of axon reflex–mediated piloerection was also attenuated in the lidocaine-treated region postiontophoresis (mean [SD], 46.2 [16.1]cm2 vs 7.2 [3.9]cm2; P.001). Piloerection was delayed in the axon reflex region compared with the direct region. Normal saline did not cause piloerection.

Conclusions: Phenylephrine provoked piloerection directly and indirectly through an axon reflex–mediated response that is attenuated by lidocaine. Piloerection is not stimulated by iontophoresis of normal saline alone.The quantitative pilomotor axon reflex test (QPART) may complement other measures of cutaneous autonomic nerve fiber function.

Background: Increasing availability of neuroimaging has facilitated the diagnosis of cerebral sinus venous thrombosis(CSVT). However, CSVT may also present with unspecific or atypical symptoms, resulting in diagnostic delay.Single reports suggested otologic symptoms as such pitfalls.

Objective: To screen patients with CSVT for otologic symptoms.

Design: Ten-year retrospective case series.

Setting: Primary and tertiary care university clinic.

Patients: Thirty-eight patients with CSVT.

Results: Of 38 patients with CSVT, 3 individuals hadacute unilateral hearing loss, 2 of which also had concomitant tinnitus and headache, and were initially treated at the ear, nose, and throat department. Magnetic resonance imaging after hospital discharge showed ipsilateral thrombosis of the lateral venous sinus. Two female patients took oral contraceptives, 1 of whom also had a heterozygous factor V Leiden mutation.

Conclusions: Cerebral sinus venous thrombosis may present with unspecific symptoms such as acute unilateral hearing loss. If in conjunction with headache or risk factors for venous thrombosis, the suspicion of ipsilateral lateral CSVT should prompt rapid imaging including venography.

Objective: To estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El Escorial criteria in several studies.

Data sources: MEDLINE and Web of Science (until October2011).

Study selection: We searched for studies testing the diagnostic accuracy of the Awaji criteria vs the revised El Escorial criteria in patients referred with suspected ALS.

Data extraction: Evaluation and data extraction of identified studies were done independently. The Quality Assessment of Diagnostic Accuracy Studies list was used to assess study quality. We determined the proportion of patients classified as having probable/definite ALS and derived indices of diagnostic performance(sensitivity, specificity, and diagnostic odds ratio). Quantitative data synthesis was accomplished through random-effects meta-analysis, and heterogeneity was assessed with the I2 test.

Data synthesis: Eight studies were included (3 prospective and 5 retrospective) enrolling 1187 patients. Application of Awaji criteria led to a 23% (95% CI, 12% to 33%; I2=84%) increase in the proportion of patients classified as having probable/definite ALS. Diagnostic performance of the Awaji criteria was higher than the revised El Escorial criteria (pooled sensitivity: 81.1% [95%CI, 72.2% to 90.0%; I2=91%] vs 62.2% [95% CI, 49.4%to 75.1%; I2=93%]; pooled diagnostic odds ratio, 35.8[95% CI, 15.2 to 84.7; I2=3%] vs 8.7 [95% CI, 2.2 to 35.6;I2=50%]). Diagnostic accuracy of Awaji criteria was higher in bulbar- than in limb-onset cases.

Conclusion: The Awaji criteria have a significant clinical impact allowing earlier diagnosis and clinical trial entry in ALS.

Background: Fingolimod (FTY720), a first-in-class sphingosine-1-phosphate (S1P) receptor agonist, is a recently approved drug for treating relapsing multiple sclerosis. Experimental evidence suggests that FTY720 not only exhibits anti-inflammatory properties but also promotes myelination in the central nervous system by direct interaction with oligodendrocytes.

Objective: To assess the effects of FTY720 on Schwann cells (SCs) and peripheral nerve myelination.

Design: Receptor expression studies and myelination were investigated in primary rat SCs and rat neuronal/SC cocultures. Cells were treated with physiologically relevant concentrations of the active phosphorylated form of FTY720 (FTY720P). In addition, S1P receptor expression was corroborated in human and rat peripheral nerve tissue sections.

Results: Schwann cells express all known S1P receptors on the RNA level, not altered by FTY720P. In the myelination model, treatment with FTY720P resulted in a significant reduction of quantitative myelin formation. FTY720P induced reactive oxygen species in SCs associated with apoptosis of these cells, as demonstrated by the detection of cysteine aspartic acid–specific protease 3 and 7, as well as terminal deoxynucleotidyl transferase dUTP nick-end labeling. This effect was dependent of S1P signaling because the blocking of S1P receptors ameliorated reactive oxygen species production, SC apoptosis, and myelin loss.

Conclusions: FTY720P at greater concentrations induces apoptosis in SCs and may interfere with peripheral nerve myelination.

Objectives: To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).

Design: Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.

Setting: Two level 1 trauma centers.

Patients: A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.

Intervention: Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.

Main outcome measures: Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.

Results: Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).

Conclusion: Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.

Trial registration: clinicaltrials.gov Identifier: NCT01463033.

A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual acuity. By the fourth decade of life, he developed poor coordination and balance, as well as inability to walk. In subsequent years, he developed progressive, painless sensory loss, weakness, and atrophy in his distal arms and legs. His vision problems progressed and he also developed dysarthria without dysphagia. Family history was negative except for an uncle who was described as "clumsy." Results of an oculomotor examination were notable for increased square-wave jerks, persistent bilateral gaze-evoked nystagmus with saccadic pursuit, intact vestibulo-ocular reflex, and saccadic dysmetria. He had a mixed dysarthria with flaccid and ataxic characteristics and severe weakness and atrophy in the distal limb muscles. Sensation was diminished to the midforearms and midthighs in all modalities. Deep tendon reflexes were absent throughout, with no response to plantar stimulation. He had marked appendicular ataxia with mild axial ataxia. Magnetic resonance imaging of the brain revealed severe cerebellar atrophy. Results of an electrodiagnostic study suggested a severe axonal sensorimotor polyneuropathy with active and chronic denervation. The differential diagnosis in a patient with ataxia, neuropathy, and oculomotor features is discussed; a methodical approach to the diagnostic workup is suggested; and the final diagnosis is revealed.