August 8 Highlights

Oculomotor markers of pre-clinical HD

Blekher et al. studied saccades in individuals at risk and recently diagnosed with Huntington disease. Presymptomatic gene carriers and individuals with early HD demonstrated abnormalities of memory-guided and antisaccades. Both increased with advancing motor signs of HD.

see page 394

Golding et al. demonstrated saccadic deficits in preclinical HD which correlated with estimates of disease progression suggesting that saccadic measures can provide an index of striatal dysfunction prior to clinical onset.

see page 485

The editorial by Biglan and Halmagyi notes that since neurodegeneration may begin long before manifest HD can be diagnosed, postponing the onset of manifest HD will require presymptomatic markers. The methods used in these two articles are simple and robust, requiring only an eye movement tracker (video, infrared, or EOG), and a computer for presenting the targets and logging measurements of latency and accuracy of saccades and antisaccades. These measures may allow for a preventive clinical trial enriched for those subjects who are relatively close to predicted onset. Studying only such individuals would enhance the power of preventive clinical trials that use disease onset as the primary outcome by allowing for smaller number of subjects followed for shorter periods of time.

see page 376

When do PD patients disclose their diagnosis?

Haines et al. found that most patients with PD disclose their diagnosis to others within 1 month, yet over 25% wait at least 1 year to disclose at work. Younger, employed men were more likely to disclose late.

see page 488

Valproate poses risk to the unborn child

Meador et al. prospectively examined fetal outcomes in pregnant women with epilepsy who were treated with monotherapy: carbamazepine, lamotrigine, phenytoin, or valproate. They found more adverse outcomes for valproate exposure vs other AEDs.

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There is a Patient Page on this topic: www.neurology.org

Sinovenous stenosis predicts idiopathic intracranial hypertension without papilledema in migraine

Figure. Two-thirds of the patients with bilateral transverse sinus stenosis had CSF pressure higher than 200 mm H₂O, while both patients with normal magnetic resonance venography and the control subjects had CSF pressures lower than 200 mm H₂O.

Bono et al. investigated the frequency of bilateral transverse sinus stenosis (BTSS) in patients with migraine to determine whether the presence of BTSS was associated with IIH without papilledema. The authors found that 6.7% of individuals with migraine had BTSS, which in two-thirds of the cases was associated with IIH.

see page 419

Intracerebral hemorrhage and pregnancy

The retrospective study by Bateman et al. showed that pregnancy-related intracerebral hemorrhage occurs more commonly in the postpartum period and accounts for 7% of all maternal deaths. Hemorrhages are associated with advanced maternal age, African American race, hypertension, preeclampsia/eclampsia, coagulopathy, and tobacco use.

see page 424

PET-beta-amyloid imaging may be marker for preclinical AD

Mintun et al. imaged beta-amyloid plaques in 41 nondemented subjects from 20 to 86 years using PET and [¹¹C]PIB. Four of the subjects over 60 years demonstrated elevated PIP uptake with two subjects having a pattern similar to that seen in AD. PET PIB scans have potential for imaging the preclinical pathologic changes of AD.

see page 446

Cognitive effects of lamotrigine vs topiramate

Blum et al. conducted a randomized, double-blind study of the cognitive effects of lamotrigine vs topiramate in patients with epilepsy. Adjunctive lamotrigine impacted cognitive function significantly less than adjunctive topiramate across standardized measures of cognition in adults with partial seizures.

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The editorial by Chadwick and Privitera notes that this study’s design highlights a number of issues about randomized controlled study (RCT) by industry. While RCTs are primarily used to examine efficacy, they can also be used to look at adverse events. However, it is unusual to see a trial in which the primary outcome is an adverse effect, namely a decline in cognitive function. This study reliably assesses one outcome (cognitive function) that would be predicted to favor lamotrigine. It has been powered to detect clinically important differences in cognitive outcomes, which can of course be detected over the short period of the study. It would have required more patients to reliably detect differences in seizure outcomes. The differences in seizure outcomes recorded are large, although not of significance. Given that there are no available studies comparing the efficacy of lamotrigine and topiramate as add-on therapy, why was the study not adequately powered to reliably detect differences in seizure outcomes? The study must not be interpreted as showing that there are no differences in efficacy between the drugs, simply because few significant differences were found on testing.

see page 378

Oral zolmitriptan in childhood migraine

A double-blind, placebo-controlled crossover study by Evers et al. showed efficacy of oral zolmitriptan 2.5 mg in childhood migraine. Zolmitriptan was as effective as ibuprofen and had only mild and transient side effects.

see page 497

Interferon–β1a (IFN β-1a) in pediatric MS

Tenembaum et al. report good tolerability to IFNβ-1a treatment in 22 of 24 children with clinically definite MS, at a dose of 22 μg, three times weekly.

see page 511

Valproate treatment for spinal muscular atrophy

In an uncontrolled trial, Weihl et al. treated seven adults with mild spinal muscular atrophy using valproate. Most showed improved strength and activities of daily living.

see page 500

Communicating with a locked-in patient

Wilhelm et al. demonstrated that a completely locked-in patient could communicate with the environment by using pH measurement in saliva with mental imagery and a pH sensor in the mouth cavity.

see page 534

The editorial by Lawrence H. Phillips notes that this situation is an example of the ethical concept of a double effect, where a medical intervention may have both an intended benefit and an unintended, but foreseeable harm. In such cases, the principle of nonmaleficence compels clinicians to weigh the moral value of both the good and bad effects of an intervention that has the potential to produce both. If improved communication devices make it more likely that patients will be at risk of becoming locked-in, the implications of the totally locked-in state must be considered. Do patients have a reasonable quality of life (QOL) in this state? Many totally locked-in patients who retain, or regain, communication ability express satisfaction with their QOL. There are, however, reports of patients who abhor the state in which they find themselves. While it is good to reopen communication with a TLI patient, before enthusiasm builds for the technology that makes it possible, the full implication of the ability to do so must be assessed. At a minimum, the QOL of the patient and the full emotional, economic, and physical impact on caregivers should be assessed.

see page 380